Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: PDK1 is a serine/threonine protein kinase. Reason: UniProt describes PDK1 as a serine/threonine kinase. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PDK1 participates in intracellular signal transduction. Reason: Insulin receptor transduction is a signal transduction pathway. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k.
GO:0008286 insulin receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: PDK1 functions in the insulin receptor signaling pathway. Reason: UniProt explicitly places PDK1 in insulin receptor transduction controlling growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. file:genes/DROME/Pdk1/Pdk1-deep-research-falcon.md In Drosophila cells, dPDK1 activates dAkt and dS6K
GO:0000166 nucleotide binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: PDK1 binds nucleotides as part of its kinase catalytic cycle. Reason: The catalytic reaction uses ATP, indicating nucleotide binding. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0004672 protein kinase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: PDK1 is a protein kinase. Reason: Protein kinase activity is supported by its serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: PDK1 is a serine/threonine protein kinase. Reason: UniProt describes PDK1 as a serine/threonine kinase. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0005524 ATP binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: PDK1 uses ATP in its catalytic reaction. Reason: The kinase reaction explicitly consumes ATP. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: PDK1 is cytoplasmic. Reason: UniProt reports cytoplasmic localization. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0006915 apoptotic process	IEA GO_REF:0000043	MODIFY	Summary: PDK1 regulates apoptosis rather than executing apoptotic processes. Reason: UniProt reports that PDK1 inhibits apoptosis; use the regulation term. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Inhibits apoptosis.
GO:0007283 spermatogenesis	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: PDK1 may participate in spermatogenesis. Reason: UniProt notes potential involvement in spermatogenesis. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt May be involved in axonal pathfinding and synaptogenesis, and in spermatogenesis.
GO:0016301 kinase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: PDK1 has kinase activity. Reason: Protein kinase function implies kinase activity. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0016740 transferase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: PDK1 is a transferase (kinase) enzyme. Reason: Kinases are transferases that transfer phosphate groups. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0030154 cell differentiation	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Cell differentiation is too general relative to the specific developmental roles reported. Reason: Evidence supports embryonic development and growth control but not a specific differentiation process. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0048638 regulation of developmental growth	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: PDK1 regulates developmental growth via insulin signaling. Reason: Insulin receptor pathway regulated by PDK1 controls growth and organ size. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: PDK1 has protein serine kinase activity. Reason: PDK1 is a serine/threonine kinase. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:1901701 cellular response to oxygen-containing compound	IEA GO_REF:0000117	UNDECIDED	Summary: Cellular response to oxygen-containing compounds is not supported by accessible evidence for PDK1. Reason: No direct evidence for this broad response term was identified in available sources. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development.
GO:0004676 3-phosphoinositide-dependent protein kinase activity	TAS Reactome:R-DME-110468	ACCEPT	Summary: PDK1 has 3-phosphoinositide-dependent protein kinase activity. Reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner. Supporting Evidence: PMID:9368760 Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2
GO:0004676 3-phosphoinositide-dependent protein kinase activity	TAS Reactome:R-DME-169827	ACCEPT	Summary: PDK1 has 3-phosphoinositide-dependent protein kinase activity. Reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner. Supporting Evidence: PMID:9368760 Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2
GO:0004674 protein serine/threonine kinase activity	IDA PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	ACCEPT	Summary: PDK1 is a serine/threonine protein kinase. Reason: UniProt describes PDK1 as a serine/threonine kinase. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development. PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ Growth by Decreased Activation of AMPK.
GO:0009898 cytoplasmic side of plasma membrane	TAS PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	KEEP AS NON CORE	Summary: PDK1 binds phosphoinositides on the cytoplasmic side of the plasma membrane. Reason: PH-domain binding to PIP3 indicates cytoplasmic membrane association. Supporting Evidence: PMID:36899949 Phosphoinositide-dependent kinase 1 (PDK1) contains a pleckstrin homology (PH) domain, which binds to Phosphatidylinositol(3,4,5)-tris-phosphate (PI(3,4,5)P3)
GO:1904262 negative regulation of TORC1 signaling	TAS PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	MARK AS OVER ANNOTATED	Summary: Negative regulation of TORC1 is not directly supported for PDK1. Reason: The cited study links AMPK to mTOR inhibition; PDK1 phosphorylation of LKB1 reduces AMPK activation, which is inconsistent with TORC1 inhibition. Supporting Evidence: PMID:36899949 Activation of AMPK by low energy supply and phosphorylation of LKB1 results in an inhibition of mTOR
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI PMID:11752451 PDK1 regulates growth through Akt and S6K in Drosophila.	KEEP AS NON CORE	Summary: PDK1 phosphorylates Akt/PKB in the PI3K-PKB pathway. Reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner. Supporting Evidence: PMID:9368760 Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2 PMID:11752451 PDK1 regulates growth through Akt and S6K in Drosophila.
GO:0046622 positive regulation of organ growth	IMP PMID:11752451 PDK1 regulates growth through Akt and S6K in Drosophila.	KEEP AS NON CORE	Summary: PDK1 promotes organ growth via insulin signaling. Reason: Insulin receptor transduction regulated by PDK1 controls organ size. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:11752451 PDK1 regulates growth through Akt and S6K in Drosophila.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:10823906 Use of double-stranded RNA interference in Drosophila cell l...	KEEP AS NON CORE	Summary: PDK1 phosphorylates Akt/PKB in the PI3K-PKB pathway. Reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner. Supporting Evidence: PMID:9368760 Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2 PMID:10823906 Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways.
GO:0045793 positive regulation of cell size	TAS Reactome:R-DME-110468	KEEP AS NON CORE	Summary: PDK1 promotes cell size via insulin signaling and S6K/Akt activation. Reason: PDK1 acts in insulin receptor signaling that regulates cell growth and size. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k.
GO:0008286 insulin receptor signaling pathway	IMP PMID:10823906 Use of double-stranded RNA interference in Drosophila cell l...	ACCEPT	Summary: PDK1 functions in the insulin receptor signaling pathway. Reason: UniProt explicitly places PDK1 in insulin receptor transduction controlling growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:10823906 Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways.
GO:0008286 insulin receptor signaling pathway	IMP PMID:14645523 Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in...	ACCEPT	Summary: PDK1 functions in the insulin receptor signaling pathway. Reason: UniProt explicitly places PDK1 in insulin receptor transduction controlling growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:14645523 Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster.
GO:0008286 insulin receptor signaling pathway	IMP PMID:16627617 TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2...	ACCEPT	Summary: PDK1 functions in the insulin receptor signaling pathway. Reason: UniProt explicitly places PDK1 in insulin receptor transduction controlling growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:16627617 TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity.
GO:0008286 insulin receptor signaling pathway	IMP PMID:29514084 Innate Immune Signaling in Drosophila Blocks Insulin Signali...	ACCEPT	Summary: PDK1 functions in the insulin receptor signaling pathway. Reason: UniProt explicitly places PDK1 in insulin receptor transduction controlling growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:29514084 Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apo...	ACCEPT	Summary: PDK1 is a serine/threonine protein kinase. Reason: UniProt describes PDK1 as a serine/threonine kinase. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Serine/threonine kinase required for embryonic development. PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.
GO:0008286 insulin receptor signaling pathway	IMP PMID:11862217 dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but ...	ACCEPT	Summary: PDK1 functions in the insulin receptor signaling pathway. Reason: UniProt explicitly places PDK1 in insulin receptor transduction controlling growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:11862217 dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1.
GO:0030307 positive regulation of cell growth	IMP PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apo...	KEEP AS NON CORE	Summary: PDK1 promotes cell growth downstream of insulin signaling. Reason: PDK1 acts in insulin receptor signaling that regulates cell growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.
GO:0030307 positive regulation of cell growth	IMP PMID:29514084 Innate Immune Signaling in Drosophila Blocks Insulin Signali...	KEEP AS NON CORE	Summary: PDK1 promotes cell growth downstream of insulin signaling. Reason: PDK1 acts in insulin receptor signaling that regulates cell growth. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:29514084 Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
GO:0040018 positive regulation of multicellular organism growth	IMP PMID:29514084 Innate Immune Signaling in Drosophila Blocks Insulin Signali...	KEEP AS NON CORE	Summary: PDK1 contributes to organismal growth downstream of insulin signaling. Reason: Insulin receptor transduction regulated by PDK1 controls growth and size. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:29514084 Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
GO:0005634 nucleus	HDA PMID:26896675 A genome-wide resource for the analysis of protein localisat...	UNDECIDED	Summary: Nuclear localization is not supported by the curated UniProt localization statement. Reason: UniProt lists cytoplasmic localization; nuclear evidence is not accessible here. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:26896675 A genome-wide resource for the analysis of protein localisation in Drosophila.
GO:0005737 cytoplasm	HDA PMID:26896675 A genome-wide resource for the analysis of protein localisat...	KEEP AS NON CORE	Summary: PDK1 is cytoplasmic. Reason: UniProt reports cytoplasmic localization. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:26896675 A genome-wide resource for the analysis of protein localisation in Drosophila.
GO:0030295 protein kinase activator activity	IDA PMID:9368760 3-Phosphoinositide-dependent protein kinase-1 (PDK1): struct...	KEEP AS NON CORE	Summary: PDK1 activates downstream protein kinases such as Akt1 and S6K. Reason: UniProt states PDK1 phosphorylates and activates Akt1 and S6K. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:9368760 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase.
GO:0046622 positive regulation of organ growth	IMP PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apo...	KEEP AS NON CORE	Summary: PDK1 promotes organ growth via insulin signaling. Reason: Insulin receptor transduction regulated by PDK1 controls organ size. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.
GO:0004676 3-phosphoinositide-dependent protein kinase activity	IDA PMID:9368760 3-Phosphoinositide-dependent protein kinase-1 (PDK1): struct...	ACCEPT	Summary: PDK1 has 3-phosphoinositide-dependent protein kinase activity. Reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner. Supporting Evidence: PMID:9368760 Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2
GO:0005829 cytosol	TAS Reactome:R-DME-110468	KEEP AS NON CORE	Summary: PDK1 localizes to the cytosol. Reason: Cytosolic localization is consistent with cytoplasmic localization. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005829 cytosol	TAS Reactome:R-DME-169827	KEEP AS NON CORE	Summary: PDK1 localizes to the cytosol. Reason: Cytosolic localization is consistent with cytoplasmic localization. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005829 cytosol	HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg...	KEEP AS NON CORE	Summary: PDK1 localizes to the cytosol. Reason: Cytosolic localization is consistent with cytoplasmic localization. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagged proteins in Drosophila embryos.
GO:0031594 neuromuscular junction	IDA PMID:21930778 S6 kinase localizes to the presynaptic active zone and funct...	KEEP AS NON CORE	Summary: PDK1 functions in synapse development at the neuromuscular junction. Reason: PDK1 works with S6K to control synapse development. Supporting Evidence: PMID:21930778 S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development.
GO:0051124 synaptic assembly at neuromuscular junction	IMP PMID:21930778 S6 kinase localizes to the presynaptic active zone and funct...	KEEP AS NON CORE	Summary: PDK1 contributes to synaptic assembly at the neuromuscular junction. Reason: PDK1 functions with S6K in synapse development at presynaptic active zones. Supporting Evidence: PMID:21930778 S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development.
GO:0045793 positive regulation of cell size	IGI PMID:19917724 A role for p38 stress-activated protein kinase in regulation...	KEEP AS NON CORE	Summary: PDK1 promotes cell size via insulin signaling and S6K/Akt activation. Reason: PDK1 acts in insulin receptor signaling that regulates cell growth and size. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:19917724 A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1.
GO:0005737 cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: PDK1 is cytoplasmic. Reason: UniProt reports cytoplasmic localization. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005886 plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: PDK1 associates with the plasma membrane via its PH domain. Reason: PDK1 binds PIP3 via its PH domain, consistent with membrane recruitment. Supporting Evidence: PMID:36899949 Phosphoinositide-dependent kinase 1 (PDK1) contains a pleckstrin homology (PH) domain, which binds to Phosphatidylinositol(3,4,5)-tris-phosphate (PI(3,4,5)P3)
GO:0007166 cell surface receptor signaling pathway	IGI PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apo...	KEEP AS NON CORE	Summary: PDK1 participates in cell surface receptor signaling (insulin receptor). Reason: Insulin receptor transduction is a cell-surface receptor signaling pathway. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.
GO:0043066 negative regulation of apoptotic process	IMP PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apo...	KEEP AS NON CORE	Summary: PDK1 inhibits apoptosis. Reason: UniProt states PDK1 inhibits apoptosis. Supporting Evidence: file:genes/DROME/Pdk1/Pdk1-uniprot.txt Inhibits apoptosis. PMID:11344272 Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.

Core Functions

PDK1 phosphorylates Akt and S6K downstream of insulin/PI3K signaling to promote growth.

Molecular Function:

3-phosphoinositide-dependent protein kinase activity

Directly Involved In:

insulin receptor signaling pathway

Supporting Evidence:

file:genes/DROME/Pdk1/Pdk1-uniprot.txt
RecName: Full=3-phosphoinositide-dependent protein kinase 1
PMID:9368760
Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2.
PMID:11752451
dPDK1 controls cellular and organism growth by activating dAkt and S6 kinase, dS6K.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10823906

Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways.

PMID:11344272

Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.

PMID:11752451

PDK1 regulates growth through Akt and S6K in Drosophila.

PMID:11862217

dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1.

PMID:14645523

Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster.

PMID:16627617

TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity.

PMID:19917724

A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1.

PMID:21930778

S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development.

PMID:25294944

Subcellular localisations of the CPTI collection of YFP-tagged proteins in Drosophila embryos.

PMID:26896675

A genome-wide resource for the analysis of protein localisation in Drosophila.

PMID:29514084

Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.

PMID:36899949

Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ Growth by Decreased Activation of AMPK.

PMID:9368760

3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase.

Reactome:R-DME-110468

Activation of DAkt1 by DPDK1

Reactome:R-DME-169827

DPDK1 phosphorylates and activates DS6K

📚 Additional Documentation

Deep Research Falcon

(Pdk1-deep-research-falcon.md)

provider: falcon
model: Edison Scientific Literature
cached: true
start_time: '2026-02-01T16:13:17.242152'
end_time: '2026-02-01T16:13:17.244575'
duration_seconds: 0.0
template_file: templates/gene_research_go_focused.md
template_variables:
organism: DROME
gene_id: Pdk1
gene_symbol: Pdk1
uniprot_accession: Q9W0V1
protein_description: 'RecName: Full=3-phosphoinositide-dependent protein kinase
1; Short=dPDK-1; EC=2.7.11.1; AltName: Full=Serine/threonine-protein kinase 61C;
AltName: Full=dSTPK61;'
gene_info: Name=Pdk1; Synonyms=Pk61C; ORFNames=CG1210;
organism_full: Drosophila melanogaster (Fruit fly).
protein_family: Belongs to the protein kinase superfamily. AGC Ser/Thr
protein_domains: Kinase-like_dom_sf. (IPR011009); PDK1-typ_PH. (IPR033931); PDPK1.
(IPR039046); PH-like_dom_sf. (IPR011993); Prot_kinase_dom. (IPR000719)
provider_config:
timeout: 600
max_retries: 3
parameters:
allowed_domains: []
temperature: 0.1
citation_count: 29

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q9W0V1
Protein Description: RecName: Full=3-phosphoinositide-dependent protein kinase 1; Short=dPDK-1; EC=2.7.11.1; AltName: Full=Serine/threonine-protein kinase 61C; AltName: Full=dSTPK61;
Gene Information: Name=Pdk1; Synonyms=Pk61C; ORFNames=CG1210;
Organism (full): Drosophila melanogaster (Fruit fly).
Protein Family: Belongs to the protein kinase superfamily. AGC Ser/Thr
Key Domains: Kinase-like_dom_sf. (IPR011009); PDK1-typ_PH. (IPR033931); PDPK1. (IPR039046); PH-like_dom_sf. (IPR011993); Prot_kinase_dom. (IPR000719)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Pdk1" matches the protein description above
Verify the organism is correct: Drosophila melanogaster (Fruit fly).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Pdk1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Pdk1 (gene ID: Pdk1, UniProt: Q9W0V1) in DROME.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q9W0V1
Protein Description: RecName: Full=3-phosphoinositide-dependent protein kinase 1; Short=dPDK-1; EC=2.7.11.1; AltName: Full=Serine/threonine-protein kinase 61C; AltName: Full=dSTPK61;
Gene Information: Name=Pdk1; Synonyms=Pk61C; ORFNames=CG1210;
Organism (full): Drosophila melanogaster (Fruit fly).
Protein Family: Belongs to the protein kinase superfamily. AGC Ser/Thr
Key Domains: Kinase-like_dom_sf. (IPR011009); PDK1-typ_PH. (IPR033931); PDPK1. (IPR039046); PH-like_dom_sf. (IPR011993); Prot_kinase_dom. (IPR000719)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Pdk1" matches the protein description above
Verify the organism is correct: Drosophila melanogaster (Fruit fly).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene Pdk1 (gene ID: Pdk1, UniProt: Q9W0V1) in DROME.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Plan status update: Identity verification is complete. We aggregated seminal Drosophila Pdk1 research and recent (2023–2024) literature, extracted mechanistic updates linking immunity and diet to Pdk1/Akt/TOR, and compiled quantitative pathway readouts. We now present a comprehensive, cited research report.

Comprehensive research report: Drosophila melanogaster Pdk1 (Pk61C/CG1210; UniProt Q9W0V1)

1) Identity, key concepts, and definitions
- Gene/protein identity: Drosophila melanogaster Pdk1 (aliases Pk61C, CG1210) encodes 3‑phosphoinositide‑dependent protein kinase 1 (dPDK1), an AGC family serine/threonine kinase orthologous to mammalian PDPK1. It functions in the canonical insulin→PI3K→PIP3 pathway, upstream of Akt/PKB and S6K, in growth control (diagrammatic placement next to PI3K and PKB) (ponce2010genòmicaevolutivade pages 62-65).
- Enzymatic role: dPDK1 is a master activation‑loop kinase for AGC kinases. In Drosophila cells, dPDK1 activates dAkt and dS6K; RNAi of dPDK1 abolishes dS6K Thr398 phosphorylation and reduces Akt activation‑loop phosphorylation in insulin‑stimulated cells (miron2003signalingfromakt pages 9-10, miron2003signalingfromakt pages 5-7).
- Substrate specificity/sites: For S6K, dPDK1 directly targets the T‑loop site equivalent to mammalian Thr389; in Drosophila, insulin‑regulated dS6K phosphorylation at Thr398 depends on PI3K/Akt and on PDK1 (biochemical and RNAi evidence) (lizcano2003insulininduceddrosophilas6 pages 1-2, miron2003signalingfromakt pages 9-10). For Akt/PKB, PDK1 phosphorylates the activation‑loop threonine (the Drosophila Akt1 site corresponds to mammalian Thr308; Drosophila literature refers to the activation‑loop site and to the hydrophobic‑motif S505; Toll‑dependent inhibition specifically reduces PDK1→Akt T342 phosphorylation in larvae, consistent with an activation‑loop target) (darby2023interactionsbetweeninnate pages 3-5, lizcano2003insulininduceddrosophilas6 pages 1-2).
- Cellular localization mechanism: PIP3 produced by PI3K recruits PH‑domain proteins to the plasma membrane; PDK1 operates at this membrane microdomain together with Akt to drive Akt activation (and to dock/activate S6K) in Drosophila cells and embryos (dekanty2005theinsulinpi3ktorpathway pages 6-8, lizcano2003insulininduceddrosophilas6 pages 1-2).

2) Role in insulin/PI3K/TOR signaling and pathway topology
- Positioning and flow: Insulin→InR→PI3K→PIP3 recruits PDK1 and Akt via PH domains; PDK1 phosphorylates Akt’s activation loop, Akt relieves TSC inhibition to permit TORC1 activation, which in turn controls S6K and 4E‑BP; PDK1 also directly phosphorylates/activates S6K on its T‑loop (lizcano2003insulininduceddrosophilas6 pages 1-2, dekanty2005theinsulinpi3ktorpathway pages 6-8, miron2003signalingfromakt pages 8-9).
- Genetic epistasis to growth: Classical Drosophila genetics established that Pdk1 regulates organismal and cellular growth through Akt and S6K; dS6K‑regulated cell growth is independent of PI3K/PKB in some contexts but requires dPDK1, placing Pdk1 as an essential node for S6K‑driven growth (ponce2010genòmicaevolutivade pages 62-65). In vivo, co‑expression of UAS‑PDK1 with PKB enhances PKB activity in fly heads; hypoxia‑induced Scylla/Charybdis reduce S6K activity upstream of TSC without altering PKB activity, consistent with the canonical placement of Pdk1 upstream of PKB and S6K (h2004thehypoxiainducedparalogs pages 7-9).
- TOR/HIF axis readouts: In embryos and S2 cells, insulin/PI3K/PDK1/Akt/TOR signaling promotes nuclear accumulation of HIF‑α/Sima and activates an HRE reporter; dPDK1 RNAi blocks insulin‑induced HRE activation, and TOR/Rheb/S6K manipulations modulate this response, embedding Pdk1 within the InR→PI3K→Akt→TOR axis (dekanty2005theinsulinpi3ktorpathway pages 6-8).

3) Recent developments (2023–2024) and latest research
- Immune–insulin crosstalk targeting PDK1→Akt: Toll pathway activation in the larval fat body inhibits PDK1 phosphorylation of Akt at T342, leading to reduced growth and triglyceride storage; forced restoration of Akt‑T342 phosphorylation in this context rescues body size and triglycerides, pinpointing the PDK1→Akt step as a functional target of immune signaling (Frontiers in Immunology, 2023; DOI:10.3389/fimmu.2023.1276357) (darby2023interactionsbetweeninnate pages 3-5).
- Diet/AA sensing: In adult females, dietary tyrosine deprivation alters 348 transcripts; insulin pathway components including Pdk1 and Akt are upregulated (RNA‑seq, Data S1), coincident with decreased phosphorylation of rpS6 (lower mTORC1 activity) and down‑regulation of Toll/IMD pathway genes—consistent with feedback within IIS and diet‑dependent immune modulation (Science Advances, 2024; DOI:10.1126/sciadv.adn7167) (kosakamoto2024contextdependentimpactof pages 7-8).
- Germline/rDNA copy number control: Insulin receptor activity represses R2 retrotransposon and regulates rDNA magnification in testes; however, RNAi inhibition of Pdk1 did not induce ectopic rDNA magnification, and mTORC1, not mTORC2, is implicated as the proximal effector controlling R2 expression; dietary restriction heightened R2 expression and magnification frequency (bioRxiv preprint, 2025; DOI:10.1101/2024.02.28.582629) (nelson2025insulinsignalingregulates pages 10-14).
- Broader expert perspectives: Authoritative reviews synthesize conserved InsR→PI3K→PIP3→PDK1→AKT→mTORC1 roles in immunity and metabolism, with PDK1 gating AKT activation and intersecting with PRR/TLR signaling (Frontiers in Endocrinology, 2023; PeerJ, 2024) (makhijani2023regulationofthe pages 3-5, murthy2024insulinsignalingand pages 6-8).

4) Enzymatic function and substrates in detail
- Akt/PKB: PDK1 phosphorylates the activation‑loop threonine of Akt following PIP3‑dependent membrane recruitment; in Drosophila larvae, the functionally critical T342 site on Akt is inhibited by Toll signaling at the level of PDK1, demonstrating physiological control of the PDK1→Akt step during immune activation (darby2023interactionsbetweeninnate pages 3-5, lizcano2003insulininduceddrosophilas6 pages 1-2).
- S6K: dS6K activation requires PI3K→PKB signaling and PDK1; insulin‑stimulated S6K phosphorylation at Thr398 is prevented by PI3K inhibition or PKB knockdown and is abolished when dPDK1 is depleted; conversely, PTEN knockdown elevates PIP3 and stimulates dS6K (Biochem J 2003) (lizcano2003insulininduceddrosophilas6 pages 1-2, miron2003signalingfromakt pages 9-10).
- 4E‑BP and TOR dependence: d4E‑BP phosphorylation is TOR‑dependent; dPDK1 knockdown reduces d4E‑BP protein levels by ~60%, but normalized insulin‑induced phosphorylation can persist, indicating differential sensitivity of downstream branches to Pdk1 levels and PI3K thresholds (Molecular and Cellular Biology 2003) (miron2003signalingfromakt pages 5-7, miron2003signalingfromakt pages 8-9).

5) Localization and domain logic
- PH‑domain/PIP3 recruitment: PI3K‑generated PIP3 recruits PH‑domain proteins to the plasma membrane, positioning Akt and PDK1 to catalyze the activation‑loop phosphorylation of Akt; in vivo overexpression studies and embryo assays support PDK1 operating at the membrane to drive AKT activation in Drosophila (J Cell Sci 2005; Biochem J 2003) (dekanty2005theinsulinpi3ktorpathway pages 6-8, lizcano2003insulininduceddrosophilas6 pages 1-2).

6) Current applications and real‑world implementations
- Genetic tools and readouts: UAS‑PDK1 co‑expression with Akt to boost PKB activity in tissue‑specific contexts; dPDK1 RNAi in S2 cells for site‑specific phosphorylation mapping (dS6K Thr398); pathway reporters (HRE‑Luc) and nuclear Sima localization to integrate insulin/PI3K/PDK1/Akt/TOR outputs in vivo; manipulation of PI3K/PTEN to tune PIP3 levels and quantify downstream phosphorylation (h2004thehypoxiainducedparalogs pages 7-9, miron2003signalingfromakt pages 9-10, dekanty2005theinsulinpi3ktorpathway pages 6-8, lizcano2003insulininduceddrosophilas6 pages 1-2).

7) Expert opinions and analysis
- Cross‑talk emphasis: Contemporary immunometabolism reviews highlight that InsR→PI3K→PDK1→AKT→mTORC1 signaling augments inflammatory programs (glycolysis, PPP, lipid synthesis) and interfaces with TLR pathways; in insects, immune pathways (Toll/IMD) can feedback to IIS at the PDK1→Akt step, providing a mechanistic basis for infection‑induced growth and metabolic reprogramming (makhijani2023regulationofthe pages 3-5, darby2023interactionsbetweeninnate pages 5-6, darby2023interactionsbetweeninnate pages 6-7).

8) Quantitative data and specific statistics
- S6K T‑loop dependence on PDK1: dPDK1 RNAi “completely” blocks dS6K Thr398 phosphorylation in S2 cells; PI3K perturbations modulate dS6K and d4E‑BP phosphorylation in opposite directions, e.g., Dp110 RNAi increased insulin‑stimulated dS6K Thr398 ~2.2‑fold, whereas dPTEN RNAi increased basal phospho‑4E‑BP ~3.4‑fold (Molecular and Cellular Biology 2003) (miron2003signalingfromakt pages 5-7).
- HIF/Sima axis: Insulin induces HRE‑Luc; dPDK1 RNAi suppresses this induction; rapamycin or dTOR/dRheb/dS6K RNAi abrogate insulin‑induced HRE activity and Sima nuclear accumulation, demonstrating quantitative dependence on the Pdk1→Akt→TOR branch (J Cell Sci 2005) (dekanty2005theinsulinpi3ktorpathway pages 6-8).
- Diet transcriptomics: Tyrosine deprivation significantly enriches FoxO/autophagy/mTOR GO terms; Pdk1 and Akt transcripts are upregulated (data S1); rpS6 phosphorylation is suppressed (Science Advances 2024) (kosakamoto2024contextdependentimpactof pages 7-8).
- Immune inhibition of Akt‑T342: Toll activation in larval fat body reduces PDK1‑mediated phosphorylation of Akt at T342; genetic restoration of T342 phosphorylation rescues body size and triglyceride storage, indicating a causative, quantitative control point at PDK1→Akt (Frontiers in Immunology 2023) (darby2023interactionsbetweeninnate pages 3-5).

9) Conclusions
Drosophila Pdk1 (Q9W0V1) encodes a conserved PDPK1 ortholog with a PH domain that localizes to PIP3‑rich membranes to phosphorylate the activation loop of Akt and the T‑loop of S6K, placing it as an essential kinase in insulin/PI3K/TOR growth control. Classical Drosophila genetics and cell biology show that Pdk1 is required for S6K Thr398 phosphorylation and for Akt activation, with differential sensitivity among downstream effectors. Recent studies reveal immune (Toll)‑mediated inhibition specifically at the PDK1→Akt activation step in the larval fat body and diet‑dependent modulation of Pdk1 expression with concomitant suppression of mTORC1 output. In the germline, InsR activity, rather than Pdk1 per se, appears to set rDNA magnification propensity via mTORC1. Together, these findings reinforce Pdk1’s central, conserved role in coupling nutrient and immune cues to growth and metabolic physiology.

Source details, URLs, and dates
- Darby & Lazzaro, 2023, Frontiers in Immunology; DOI:10.3389/fimmu.2023.1276357; URL: https://doi.org/10.3389/fimmu.2023.1276357 (darby2023interactionsbetweeninnate pages 5-6, darby2023interactionsbetweeninnate pages 6-7, darby2023interactionsbetweeninnate pages 3-5).
- Kosakamoto et al., 2024, Science Advances; DOI:10.1126/sciadv.adn7167; URL: https://doi.org/10.1126/sciadv.adn7167 (kosakamoto2024contextdependentimpactof pages 7-8).
- Murthy et al., 2024, PeerJ; DOI:10.7717/peerj.16804; URL: https://doi.org/10.7717/peerj.16804 (murthy2024insulinsignalingand pages 6-8).
- Makhijani et al., 2023, Frontiers in Endocrinology; DOI:10.3389/fendo.2023.1128622; URL: https://doi.org/10.3389/fendo.2023.1128622 (makhijani2023regulationofthe pages 3-5).
- Miron et al., 2003, Mol Cell Biol; DOI:10.1128/MCB.23.24.9117-9126.2003; URL: https://doi.org/10.1128/mcb.23.24.9117-9126.2003 (miron2003signalingfromakt pages 9-10, miron2003signalingfromakt pages 5-7, miron2003signalingfromakt pages 8-9).
- Lizcano et al., 2003, Biochem J; DOI:10.1042/BJ20030577; URL: https://doi.org/10.1042/BJ20030577 (lizcano2003insulininduceddrosophilas6 pages 1-2).
- Reiling & Hafen, 2004, Genes Dev; DOI:10.1101/gad.322704; URL: https://doi.org/10.1101/gad.322704 (h2004thehypoxiainducedparalogs pages 7-9).
- Dekanty et al., 2005, J Cell Sci; DOI:10.1242/jcs.02648; URL: https://doi.org/10.1242/jcs.02648 (dekanty2005theinsulinpi3ktorpathway pages 6-8).
- Álvarez Ponce, 2010, insulin/TOR pathway evolution in insects/vertebrates; schematic and genetic placement of PDK1; URL: not provided in excerpt (ponce2010genòmicaevolutivade pages 62-65).
- Nelson et al., 2025, bioRxiv preprint; DOI:10.1101/2024.02.28.582629; URL: https://doi.org/10.1101/2024.02.28.582629 (nelson2025insulinsignalingregulates pages 10-14).

References

(ponce2010genòmicaevolutivade pages 62-65): D Álvarez Ponce. Genòmica evolutiva de la via de transducció de senyal de la insulina/tor a insectes i vertebrats. Unknown journal, 2010.
(miron2003signalingfromakt pages 9-10): Mathieu Miron, Paul Lasko, and Nahum Sonenberg. Signaling from akt to frap/tor targets both 4e-bp ands6k in drosophilamelanogaster. Molecular and Cellular Biology, 23:9117-9126, Dec 2003. URL: https://doi.org/10.1128/mcb.23.24.9117-9126.2003, doi:10.1128/mcb.23.24.9117-9126.2003. This article has 170 citations and is from a domain leading peer-reviewed journal.
(miron2003signalingfromakt pages 5-7): Mathieu Miron, Paul Lasko, and Nahum Sonenberg. Signaling from akt to frap/tor targets both 4e-bp ands6k in drosophilamelanogaster. Molecular and Cellular Biology, 23:9117-9126, Dec 2003. URL: https://doi.org/10.1128/mcb.23.24.9117-9126.2003, doi:10.1128/mcb.23.24.9117-9126.2003. This article has 170 citations and is from a domain leading peer-reviewed journal.
(lizcano2003insulininduceddrosophilas6 pages 1-2): Jose M. LIZCANO, Saif ALRUBAIE, Agnieszka KIELOCH, Maria DEAK, Sally J. LEEVERS, and Dario R. ALESSI. Insulin-induced drosophila s6 kinase activation requires phosphoinositide 3-kinase and protein kinase b. The Biochemical journal, 374 Pt 2:297-306, Sep 2003. URL: https://doi.org/10.1042/bj20030577, doi:10.1042/bj20030577. This article has 91 citations.
(darby2023interactionsbetweeninnate pages 3-5): Andrea M. Darby and Brian P. Lazzaro. Interactions between innate immunity and insulin signaling affect resistance to infection in insects. Frontiers in Immunology, Oct 2023. URL: https://doi.org/10.3389/fimmu.2023.1276357, doi:10.3389/fimmu.2023.1276357. This article has 14 citations and is from a peer-reviewed journal.
(dekanty2005theinsulinpi3ktorpathway pages 6-8): Andrés Dekanty, Sofía Lavista-Llanos, Maximiliano Irisarri, Sean Oldham, and Pablo Wappner. The insulin-pi3k/tor pathway induces a hif-dependent transcriptional response in drosophila by promoting nuclear localization of hif-α/sima. Journal of Cell Science, 118:5431-5441, Dec 2005. URL: https://doi.org/10.1242/jcs.02648, doi:10.1242/jcs.02648. This article has 136 citations and is from a domain leading peer-reviewed journal.
(miron2003signalingfromakt pages 8-9): Mathieu Miron, Paul Lasko, and Nahum Sonenberg. Signaling from akt to frap/tor targets both 4e-bp ands6k in drosophilamelanogaster. Molecular and Cellular Biology, 23:9117-9126, Dec 2003. URL: https://doi.org/10.1128/mcb.23.24.9117-9126.2003, doi:10.1128/mcb.23.24.9117-9126.2003. This article has 170 citations and is from a domain leading peer-reviewed journal.
(h2004thehypoxiainducedparalogs pages 7-9): J H Reiling and E Hafen. The hypoxia-induced paralogs scylla and charybdis inhibit growth by down-regulating s6k activity upstream of tsc in drosophila. Genes & development, 18 23:2879-92, Dec 2004. URL: https://doi.org/10.1101/gad.322704, doi:10.1101/gad.322704. This article has 399 citations and is from a highest quality peer-reviewed journal.
(kosakamoto2024contextdependentimpactof pages 7-8): Hina Kosakamoto, Chisako Sakuma, Rina Okada, Masayuki Miura, and Fumiaki Obata. Context-dependent impact of the dietary non-essential amino acid tyrosine on drosophila physiology and longevity. Science Advances, Aug 2024. URL: https://doi.org/10.1126/sciadv.adn7167, doi:10.1126/sciadv.adn7167. This article has 14 citations and is from a highest quality peer-reviewed journal.
(nelson2025insulinsignalingregulates pages 10-14): Jonathan O. Nelson, Alyssa Slicko, Amelie A Raz, and Yukiko M. Yamashita. Insulin signaling regulates r2 retrotransposon expression to orchestrate transgenerational rdna copy number maintenance. bioRxiv, Feb 2025. URL: https://doi.org/10.1101/2024.02.28.582629, doi:10.1101/2024.02.28.582629. This article has 1 citations and is from a poor quality or predatory journal.
(makhijani2023regulationofthe pages 3-5): Priya Makhijani, Paulo José Basso, Yi Tao Chan, Nan Chen, Jordan Baechle, Saad Khan, David Furman, Sue Tsai, and Daniel A. Winer. Regulation of the immune system by the insulin receptor in health and disease. Frontiers in Endocrinology, Mar 2023. URL: https://doi.org/10.3389/fendo.2023.1128622, doi:10.3389/fendo.2023.1128622. This article has 61 citations and is from a poor quality or predatory journal.
(murthy2024insulinsignalingand pages 6-8): Meghana Hosahalli Shivananda Murthy, Paniz Jasbi, Whitney Lowe, Lokender Kumar, Monsurat Olaosebikan, Liza Roger, Jinkyu Yang, Nastassja Lewinski, Noah Daniels, Lenore Cowen, and Judith Klein-Seetharaman. Insulin signaling and pharmacology in humans and in corals. PeerJ, 12:e16804, Jan 2024. URL: https://doi.org/10.7717/peerj.16804, doi:10.7717/peerj.16804. This article has 4 citations and is from a peer-reviewed journal.
(darby2023interactionsbetweeninnate pages 5-6): Andrea M. Darby and Brian P. Lazzaro. Interactions between innate immunity and insulin signaling affect resistance to infection in insects. Frontiers in Immunology, Oct 2023. URL: https://doi.org/10.3389/fimmu.2023.1276357, doi:10.3389/fimmu.2023.1276357. This article has 14 citations and is from a peer-reviewed journal.
(darby2023interactionsbetweeninnate pages 6-7): Andrea M. Darby and Brian P. Lazzaro. Interactions between innate immunity and insulin signaling affect resistance to infection in insects. Frontiers in Immunology, Oct 2023. URL: https://doi.org/10.3389/fimmu.2023.1276357, doi:10.3389/fimmu.2023.1276357. This article has 14 citations and is from a peer-reviewed journal.

Citations

h2004thehypoxiainducedparalogs pages 7-9
darby2023interactionsbetweeninnate pages 3-5
kosakamoto2024contextdependentimpactof pages 7-8
nelson2025insulinsignalingregulates pages 10-14
miron2003signalingfromakt pages 5-7
murthy2024insulinsignalingand pages 6-8
makhijani2023regulationofthe pages 3-5
miron2003signalingfromakt pages 9-10
miron2003signalingfromakt pages 8-9
darby2023interactionsbetweeninnate pages 5-6
darby2023interactionsbetweeninnate pages 6-7
https://doi.org/10.3389/fimmu.2023.1276357
https://doi.org/10.1126/sciadv.adn7167
https://doi.org/10.7717/peerj.16804
https://doi.org/10.3389/fendo.2023.1128622
https://doi.org/10.1128/mcb.23.24.9117-9126.2003
https://doi.org/10.1042/BJ20030577
https://doi.org/10.1101/gad.322704
https://doi.org/10.1242/jcs.02648
https://doi.org/10.1101/2024.02.28.582629
https://doi.org/10.1128/mcb.23.24.9117-9126.2003,
https://doi.org/10.1042/bj20030577,
https://doi.org/10.3389/fimmu.2023.1276357,
https://doi.org/10.1242/jcs.02648,
https://doi.org/10.1101/gad.322704,
https://doi.org/10.1126/sciadv.adn7167,
https://doi.org/10.1101/2024.02.28.582629,
https://doi.org/10.3389/fendo.2023.1128622,
https://doi.org/10.7717/peerj.16804,

📄 View Raw YAML

id: Q9W0V1
gene_symbol: Pdk1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: '3-phosphoinositide-dependent protein kinase 1 that activates Akt and
  S6K downstream of insulin/PI3K signaling to drive growth.'
alternative_products:
- name: 4 (D)
  id: Q9W0V1-4
- name: 1 (C)
  id: Q9W0V1-1
  sequence_note: VSP_017083
- name: 2 (A, F)
  id: Q9W0V1-2
  sequence_note: VSP_004896
- name: 3 (B, E)
  id: Q9W0V1-3
  sequence_note: VSP_004897
existing_annotations:
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review: &id001
    summary: PDK1 is a serine/threonine protein kinase.
    action: ACCEPT
    reason: UniProt describes PDK1 as a serine/threonine kinase.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PDK1 participates in intracellular signal transduction.
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor transduction is a signal transduction pathway.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PDK1 functions in the insulin receptor signaling pathway.
    action: ACCEPT
    reason: UniProt explicitly places PDK1 in insulin receptor transduction 
      controlling growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: file:genes/DROME/Pdk1/Pdk1-deep-research-falcon.md
      supporting_text: In Drosophila cells, dPDK1 activates dAkt and dS6K
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PDK1 binds nucleotides as part of its kinase catalytic cycle.
    action: KEEP_AS_NON_CORE
    reason: The catalytic reaction uses ATP, indicating nucleotide binding.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: PDK1 is a protein kinase.
    action: KEEP_AS_NON_CORE
    reason: Protein kinase activity is supported by its serine/threonine kinase 
      function.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review: *id001
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: PDK1 uses ATP in its catalytic reaction.
    action: KEEP_AS_NON_CORE
    reason: The kinase reaction explicitly consumes ATP.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review: &id004
    summary: PDK1 is cytoplasmic.
    action: KEEP_AS_NON_CORE
    reason: UniProt reports cytoplasmic localization.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PDK1 regulates apoptosis rather than executing apoptotic processes.
    action: MODIFY
    reason: UniProt reports that PDK1 inhibits apoptosis; use the regulation 
      term.
    proposed_replacement_terms:
    - id: GO:0043066
      label: negative regulation of apoptotic process
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Inhibits apoptosis.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PDK1 may participate in spermatogenesis.
    action: KEEP_AS_NON_CORE
    reason: UniProt notes potential involvement in spermatogenesis.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: May be involved in axonal pathfinding and synaptogenesis,
        and in spermatogenesis.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PDK1 has kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Protein kinase function implies kinase activity.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PDK1 is a transferase (kinase) enzyme.
    action: KEEP_AS_NON_CORE
    reason: Kinases are transferases that transfer phosphate groups.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Cell differentiation is too general relative to the specific 
      developmental roles reported.
    action: MARK_AS_OVER_ANNOTATED
    reason: Evidence supports embryonic development and growth control but not a
      specific differentiation process.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:0048638
    label: regulation of developmental growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: PDK1 regulates developmental growth via insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor pathway regulated by PDK1 controls growth and organ
      size.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: PDK1 has protein serine kinase activity.
    action: KEEP_AS_NON_CORE
    reason: PDK1 is a serine/threonine kinase.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:1901701
    label: cellular response to oxygen-containing compound
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Cellular response to oxygen-containing compounds is not supported 
      by accessible evidence for PDK1.
    action: UNDECIDED
    reason: No direct evidence for this broad response term was identified in 
      available sources.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
- term:
    id: GO:0004676
    label: 3-phosphoinositide-dependent protein kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-DME-110468
  review: &id002
    summary: PDK1 has 3-phosphoinositide-dependent protein kinase activity.
    action: ACCEPT
    reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner.
    supported_by:
    - reference_id: PMID:9368760
      supporting_text: Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB 
        alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2
- term:
    id: GO:0004676
    label: 3-phosphoinositide-dependent protein kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-DME-169827
  review: *id002
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:36899949
  review:
    summary: PDK1 is a serine/threonine protein kinase.
    action: ACCEPT
    reason: UniProt describes PDK1 as a serine/threonine kinase.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
    - reference_id: PMID:36899949
      supporting_text: Phosphorylation of LKB1 by PDK1 Inhibits Cell 
        Proliferation and Organ Growth by Decreased Activation of AMPK.
- term:
    id: GO:0009898
    label: cytoplasmic side of plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:36899949
  review:
    summary: PDK1 binds phosphoinositides on the cytoplasmic side of the plasma 
      membrane.
    action: KEEP_AS_NON_CORE
    reason: PH-domain binding to PIP3 indicates cytoplasmic membrane 
      association.
    supported_by:
    - reference_id: PMID:36899949
      supporting_text: Phosphoinositide-dependent kinase 1 (PDK1) contains a 
        pleckstrin homology (PH) domain, which binds to 
        Phosphatidylinositol(3,4,5)-tris-phosphate (PI(3,4,5)P3)
- term:
    id: GO:1904262
    label: negative regulation of TORC1 signaling
  evidence_type: TAS
  original_reference_id: PMID:36899949
  review:
    summary: Negative regulation of TORC1 is not directly supported for PDK1.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cited study links AMPK to mTOR inhibition; PDK1 phosphorylation 
      of LKB1 reduces AMPK activation, which is inconsistent with TORC1 
      inhibition.
    supported_by:
    - reference_id: PMID:36899949
      supporting_text: Activation of AMPK by low energy supply and 
        phosphorylation of LKB1 results in an inhibition of mTOR
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IGI
  original_reference_id: PMID:11752451
  review:
    summary: PDK1 phosphorylates Akt/PKB in the PI3K-PKB pathway.
    action: KEEP_AS_NON_CORE
    reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner.
    supported_by:
    - reference_id: PMID:9368760
      supporting_text: Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB 
        alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2
    - reference_id: PMID:11752451
      supporting_text: PDK1 regulates growth through Akt and S6K in Drosophila.
- term:
    id: GO:0046622
    label: positive regulation of organ growth
  evidence_type: IMP
  original_reference_id: PMID:11752451
  review:
    summary: PDK1 promotes organ growth via insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor transduction regulated by PDK1 controls organ size.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:11752451
      supporting_text: PDK1 regulates growth through Akt and S6K in Drosophila.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IMP
  original_reference_id: PMID:10823906
  review:
    summary: PDK1 phosphorylates Akt/PKB in the PI3K-PKB pathway.
    action: KEEP_AS_NON_CORE
    reason: PDK1 phosphorylates PKB/Akt in a phosphoinositide-dependent manner.
    supported_by:
    - reference_id: PMID:9368760
      supporting_text: Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB 
        alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2
    - reference_id: PMID:10823906
      supporting_text: Use of double-stranded RNA interference in Drosophila 
        cell lines to dissect signal transduction pathways.
- term:
    id: GO:0045793
    label: positive regulation of cell size
  evidence_type: TAS
  original_reference_id: Reactome:R-DME-110468
  review:
    summary: PDK1 promotes cell size via insulin signaling and S6K/Akt 
      activation.
    action: KEEP_AS_NON_CORE
    reason: PDK1 acts in insulin receptor signaling that regulates cell growth 
      and size.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:10823906
  review:
    summary: PDK1 functions in the insulin receptor signaling pathway.
    action: ACCEPT
    reason: UniProt explicitly places PDK1 in insulin receptor transduction 
      controlling growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:10823906
      supporting_text: Use of double-stranded RNA interference in Drosophila 
        cell lines to dissect signal transduction pathways.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:14645523
  review:
    summary: PDK1 functions in the insulin receptor signaling pathway.
    action: ACCEPT
    reason: UniProt explicitly places PDK1 in insulin receptor transduction 
      controlling growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:14645523
      supporting_text: Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K
        in Drosophila melanogaster.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:16627617
  review:
    summary: PDK1 functions in the insulin receptor signaling pathway.
    action: ACCEPT
    reason: UniProt explicitly places PDK1 in insulin receptor transduction 
      controlling growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:16627617
      supporting_text: TSC1/TSC2 and Rheb have different effects on TORC1 and 
        TORC2 activity.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:29514084
  review:
    summary: PDK1 functions in the insulin receptor signaling pathway.
    action: ACCEPT
    reason: UniProt explicitly places PDK1 in insulin receptor transduction 
      controlling growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:29514084
      supporting_text: Innate Immune Signaling in Drosophila Blocks Insulin 
        Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11344272
  review:
    summary: PDK1 is a serine/threonine protein kinase.
    action: ACCEPT
    reason: UniProt describes PDK1 as a serine/threonine kinase.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Serine/threonine kinase required for embryonic 
        development.
    - reference_id: PMID:11344272
      supporting_text: Drosophila phosphoinositide-dependent kinase-1 regulates 
        apoptosis and growth via the phosphoinositide 3-kinase-dependent 
        signaling pathway.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:11862217
  review:
    summary: PDK1 functions in the insulin receptor signaling pathway.
    action: ACCEPT
    reason: UniProt explicitly places PDK1 in insulin receptor transduction 
      controlling growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:11862217
      supporting_text: dS6K-regulated cell growth is dPKB/dPI(3)K-independent, 
        but requires dPDK1.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: IMP
  original_reference_id: PMID:11344272
  review:
    summary: PDK1 promotes cell growth downstream of insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: PDK1 acts in insulin receptor signaling that regulates cell growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:11344272
      supporting_text: Drosophila phosphoinositide-dependent kinase-1 regulates 
        apoptosis and growth via the phosphoinositide 3-kinase-dependent 
        signaling pathway.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: IMP
  original_reference_id: PMID:29514084
  review:
    summary: PDK1 promotes cell growth downstream of insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: PDK1 acts in insulin receptor signaling that regulates cell growth.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:29514084
      supporting_text: Innate Immune Signaling in Drosophila Blocks Insulin 
        Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
- term:
    id: GO:0040018
    label: positive regulation of multicellular organism growth
  evidence_type: IMP
  original_reference_id: PMID:29514084
  review:
    summary: PDK1 contributes to organismal growth downstream of insulin 
      signaling.
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor transduction regulated by PDK1 controls growth and 
      size.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:29514084
      supporting_text: Innate Immune Signaling in Drosophila Blocks Insulin 
        Signaling by Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:26896675
  review:
    summary: Nuclear localization is not supported by the curated UniProt 
      localization statement.
    action: UNDECIDED
    reason: UniProt lists cytoplasmic localization; nuclear evidence is not 
      accessible here.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
    - reference_id: PMID:26896675
      supporting_text: A genome-wide resource for the analysis of protein 
        localisation in Drosophila.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:26896675
  review:
    summary: PDK1 is cytoplasmic.
    action: KEEP_AS_NON_CORE
    reason: UniProt reports cytoplasmic localization.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
    - reference_id: PMID:26896675
      supporting_text: A genome-wide resource for the analysis of protein 
        localisation in Drosophila.
- term:
    id: GO:0030295
    label: protein kinase activator activity
  evidence_type: IDA
  original_reference_id: PMID:9368760
  review:
    summary: PDK1 activates downstream protein kinases such as Akt1 and S6K.
    action: KEEP_AS_NON_CORE
    reason: UniProt states PDK1 phosphorylates and activates Akt1 and S6K.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:9368760
      supporting_text: '3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural
        and functional homology with the Drosophila DSTPK61 kinase.'
- term:
    id: GO:0046622
    label: positive regulation of organ growth
  evidence_type: IMP
  original_reference_id: PMID:11344272
  review:
    summary: PDK1 promotes organ growth via insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor transduction regulated by PDK1 controls organ size.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:11344272
      supporting_text: Drosophila phosphoinositide-dependent kinase-1 regulates 
        apoptosis and growth via the phosphoinositide 3-kinase-dependent 
        signaling pathway.
- term:
    id: GO:0004676
    label: 3-phosphoinositide-dependent protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:9368760
  review: *id002
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-DME-110468
  review: &id003
    summary: PDK1 localizes to the cytosol.
    action: KEEP_AS_NON_CORE
    reason: Cytosolic localization is consistent with cytoplasmic localization.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-DME-169827
  review: *id003
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:25294944
  review:
    summary: PDK1 localizes to the cytosol.
    action: KEEP_AS_NON_CORE
    reason: Cytosolic localization is consistent with cytoplasmic localization.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
    - reference_id: PMID:25294944
      supporting_text: Subcellular localisations of the CPTI collection of 
        YFP-tagged proteins in Drosophila embryos.
- term:
    id: GO:0031594
    label: neuromuscular junction
  evidence_type: IDA
  original_reference_id: PMID:21930778
  review:
    summary: PDK1 functions in synapse development at the neuromuscular 
      junction.
    action: KEEP_AS_NON_CORE
    reason: PDK1 works with S6K to control synapse development.
    supported_by:
    - reference_id: PMID:21930778
      supporting_text: S6 kinase localizes to the presynaptic active zone and 
        functions with PDK1 to control synapse development.
- term:
    id: GO:0051124
    label: synaptic assembly at neuromuscular junction
  evidence_type: IMP
  original_reference_id: PMID:21930778
  review:
    summary: PDK1 contributes to synaptic assembly at the neuromuscular 
      junction.
    action: KEEP_AS_NON_CORE
    reason: PDK1 functions with S6K in synapse development at presynaptic active
      zones.
    supported_by:
    - reference_id: PMID:21930778
      supporting_text: S6 kinase localizes to the presynaptic active zone and 
        functions with PDK1 to control synapse development.
- term:
    id: GO:0045793
    label: positive regulation of cell size
  evidence_type: IGI
  original_reference_id: PMID:19917724
  review:
    summary: PDK1 promotes cell size via insulin signaling and S6K/Akt 
      activation.
    action: KEEP_AS_NON_CORE
    reason: PDK1 acts in insulin receptor signaling that regulates cell growth 
      and size.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:19917724
      supporting_text: A role for p38 stress-activated protein kinase in 
        regulation of cell growth via TORC1.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review: *id004
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: PDK1 associates with the plasma membrane via its PH domain.
    action: KEEP_AS_NON_CORE
    reason: PDK1 binds PIP3 via its PH domain, consistent with membrane 
      recruitment.
    supported_by:
    - reference_id: PMID:36899949
      supporting_text: Phosphoinositide-dependent kinase 1 (PDK1) contains a 
        pleckstrin homology (PH) domain, which binds to 
        Phosphatidylinositol(3,4,5)-tris-phosphate (PI(3,4,5)P3)
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:11344272
  review:
    summary: PDK1 participates in cell surface receptor signaling (insulin 
      receptor).
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor transduction is a cell-surface receptor signaling 
      pathway.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Acts in the insulin receptor transduction pathway which 
        regulates cell growth and organ size, by phosphorylating and activating 
        Akt1 and S6k.
    - reference_id: PMID:11344272
      supporting_text: Drosophila phosphoinositide-dependent kinase-1 regulates 
        apoptosis and growth via the phosphoinositide 3-kinase-dependent 
        signaling pathway.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:11344272
  review:
    summary: PDK1 inhibits apoptosis.
    action: KEEP_AS_NON_CORE
    reason: UniProt states PDK1 inhibits apoptosis.
    supported_by:
    - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
      supporting_text: Inhibits apoptosis.
    - reference_id: PMID:11344272
      supporting_text: Drosophila phosphoinositide-dependent kinase-1 regulates 
        apoptosis and growth via the phosphoinositide 3-kinase-dependent 
        signaling pathway.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10823906
  title: Use of double-stranded RNA interference in Drosophila cell lines to 
    dissect signal transduction pathways.
  findings: []
- id: PMID:11344272
  title: Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and 
    growth via the phosphoinositide 3-kinase-dependent signaling pathway.
  findings: []
- id: PMID:11752451
  title: PDK1 regulates growth through Akt and S6K in Drosophila.
  findings: []
- id: PMID:11862217
  title: dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires 
    dPDK1.
  findings: []
- id: PMID:14645523
  title: Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila
    melanogaster.
  findings: []
- id: PMID:16627617
  title: TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity.
  findings: []
- id: PMID:19917724
  title: A role for p38 stress-activated protein kinase in regulation of cell 
    growth via TORC1.
  findings: []
- id: PMID:21930778
  title: S6 kinase localizes to the presynaptic active zone and functions with 
    PDK1 to control synapse development.
  findings: []
- id: PMID:25294944
  title: Subcellular localisations of the CPTI collection of YFP-tagged proteins
    in Drosophila embryos.
  findings: []
- id: PMID:26896675
  title: A genome-wide resource for the analysis of protein localisation in 
    Drosophila.
  findings: []
- id: PMID:29514084
  title: Innate Immune Signaling in Drosophila Blocks Insulin Signaling by 
    Uncoupling PI(3,4,5)P(3) Production and Akt Activation.
  findings: []
- id: PMID:36899949
  title: Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ 
    Growth by Decreased Activation of AMPK.
  findings: []
- id: PMID:9368760
  title: '3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional
    homology with the Drosophila DSTPK61 kinase.'
  findings: []
- id: Reactome:R-DME-110468
  title: Activation of DAkt1 by DPDK1
  findings: []
- id: Reactome:R-DME-169827
  title: DPDK1 phosphorylates and activates DS6K
  findings: []
core_functions:
- description: PDK1 phosphorylates Akt and S6K downstream of insulin/PI3K 
    signaling to promote growth.
  supported_by:
  - reference_id: file:genes/DROME/Pdk1/Pdk1-uniprot.txt
    supporting_text: 'RecName: Full=3-phosphoinositide-dependent protein kinase 1'
  - reference_id: PMID:9368760
    supporting_text: Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB 
      alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2.
  - reference_id: PMID:11752451
    supporting_text: dPDK1 controls cellular and organism growth by activating 
      dAkt and S6 kinase, dS6K.
  molecular_function:
    id: GO:0004676
    label: 3-phosphoinositide-dependent protein kinase activity
  directly_involved_in:
  - id: GO:0008286
    label: insulin receptor signaling pathway

Pdk1

Gene Description

Existing Annotations Review

Core Functions

PDK1 phosphorylates Akt and S6K downstream of insulin/PI3K signaling to promote growth.

References

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

📄 View Raw YAML