Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: LKB1 is a serine/threonine protein kinase. Reason: UniProt catalytic activity indicates serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) file:genes/DROME/Lkb1/Lkb1-deep-research-falcon.md RecName: Full=Serine/threonine-protein kinase STK11
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: LKB1 localizes to the cytoplasm. Reason: UniProt lists cytoplasmic localization. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256\|ARBA:ARBA00004496}.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: LKB1 participates in intracellular signal transduction via AMPK-related kinases. Reason: Regulation of AMPK-family kinases places LKB1 in intracellular signaling pathways. Supporting Evidence: PMID:25996931 LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases
GO:0000166 nucleotide binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: LKB1 binds nucleotides as part of its kinase reaction. Reason: The catalytic reaction uses ATP, indicating nucleotide binding. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0001558 regulation of cell growth	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: LKB1 regulates organ growth through apoptosis signaling. Reason: LKB1 negatively regulates organ growth via apoptosis. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis
GO:0004672 protein kinase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: LKB1 has protein kinase activity. Reason: Catalytic activity confirms protein kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: LKB1 is a serine/threonine protein kinase. Reason: UniProt catalytic activity indicates serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0005524 ATP binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: LKB1 uses ATP in its catalytic reaction. Reason: The kinase reaction explicitly consumes ATP. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: LKB1 can localize to the nucleus per UniProt annotation. Reason: UniProt lists nucleus as a subcellular location. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256\|ARBA:ARBA00004496}. Nucleus
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: LKB1 localizes to the cytoplasm. Reason: UniProt lists cytoplasmic localization. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256\|ARBA:ARBA00004496}.
GO:0006915 apoptotic process	IEA GO_REF:0000043	MODIFY	Summary: LKB1 regulates apoptosis rather than being a core apoptotic machinery component. Reason: LKB1 induces apoptosis via JNK signaling; use positive regulation of apoptotic process. Proposed replacements: positive regulation of apoptotic process Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis
GO:0006974 DNA damage response	IEA GO_REF:0000043	UNDECIDED	Summary: DNA damage response is not supported by the accessible sources. Reason: No direct DNA damage response evidence was found in the available abstracts. Supporting Evidence: PMID:17507418 mutations disrupt spindle formation, resulting in frequent polyploid cells in larval brains
GO:0016301 kinase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: LKB1 has kinase activity. Reason: Catalytic activity confirms kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0016740 transferase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: LKB1 is a transferase (kinase) enzyme. Reason: Kinases transfer phosphate groups from ATP. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0030010 establishment of cell polarity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: LKB1 is required for cell polarity establishment. Reason: Lkb1 is required for oocyte A-P polarity and epithelial polarity. Supporting Evidence: PMID:12540903 homologue, lkb1, is required for the early A-P polarity of the oocyte
GO:0030295 protein kinase activator activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: LKB1 activates AMPK and related kinases. Reason: LKB1 regulates AMPK and other AMPK-related kinases. Supporting Evidence: PMID:25996931 LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases
GO:0042593 glucose homeostasis	IEA GO_REF:0000002	UNDECIDED	Summary: Glucose homeostasis is not directly supported by the accessible evidence. Reason: Available sources focus on lipid metabolism and polarity rather than glucose homeostasis. Supporting Evidence: PMID:25996931 LKB1 mutants display decreased lipid storage and increased gene expression of brummer
GO:0046872 metal ion binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: LKB1 binds divalent metal ions required for catalysis. Reason: UniProt lists Mg2+ and Mn2+ as cofactors. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt Name=Mg(2+) file:genes/DROME/Lkb1/Lkb1-uniprot.txt Name=Mn(2+)
GO:0008284 positive regulation of cell population proliferation	IMP PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	MARK AS OVER ANNOTATED	Summary: Positive regulation of cell proliferation is not supported for LKB1. Reason: LKB1 acts as a tumor suppressor and restricts growth; the cited study links LKB1 inhibition to increased growth. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis 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	IDA PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	KEEP AS NON CORE	Summary: LKB1 association with membranes is noted in the PDK1 interaction study. Reason: PDK1-mediated regulation of LKB1 involves membrane-associated interactions. Supporting Evidence: PMID:36899949 phosphorylation of LKB1 by PDK1 results in an inhibition of LKB1, decreased activation of AMPK and enhanced cell growth
GO:0043539 protein serine/threonine kinase activator activity	IDA PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	KEEP AS NON CORE	Summary: LKB1 activates serine/threonine kinases such as AMPK/SIKs. Reason: LKB1 regulates AMPK and other AMPK-related kinases. Supporting Evidence: PMID:25996931 LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ Growth by Decreased Activation of AMPK.
GO:1904263 positive regulation of TORC1 signaling	IMP PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ...	MODIFY	Summary: Positive regulation of TORC1 signaling is inconsistent with LKB1–AMPK inhibition of mTOR. Reason: AMPK activation downstream of LKB1 inhibits mTOR; use negative regulation of TORC1 signaling instead. Proposed replacements: negative regulation of TORC1 signaling Supporting Evidence: PMID:36899949 Activation of AMPK by low energy supply and phosphorylation of LKB1 results in an inhibition of mTOR
GO:0007291 sperm individualization	IMP PMID:28767695 Drosophila LKB1 is required for the assembly of the polarize...	KEEP AS NON CORE	Summary: LKB1 is required for spermatid individualization. Reason: LKB1 is required for actin cone formation enabling spermatid individualization. Supporting Evidence: PMID:28767695 dLKB1 is required in the germline for the formation of the actin cone, the polarized structure that allows spermatid individualization
GO:0004674 protein serine/threonine kinase activity	IMP PMID:25996931 Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathwa...	ACCEPT	Summary: LKB1 is a serine/threonine protein kinase. Reason: UniProt catalytic activity indicates serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) PMID:25996931 Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in Drosophila.
GO:0010897 negative regulation of triglyceride catabolic process	IMP PMID:25996931 Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathwa...	KEEP AS NON CORE	Summary: LKB1 suppresses lipolysis and supports lipid storage. Reason: LKB1 mutants show decreased lipid storage and increased lipase expression. Supporting Evidence: PMID:25996931 LKB1 mutants display decreased lipid storage and increased gene expression of brummer
GO:0005515 protein binding	IPI PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli...	UNDECIDED	Summary: Protein binding evidence is not explicit in the available abstract for this annotation. Reason: The endosomal regulation study does not explicitly document LKB1 binding partners in the abstract. Supporting Evidence: PMID:29084199 dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11)
GO:0005768 endosome	IDA PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli...	KEEP AS NON CORE	Summary: LKB1 localizes to endosomes in epithelial cells. Reason: Endosomal LKB1 localization is reported in epithelial integrity studies. Supporting Evidence: PMID:29084199 dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11)
GO:0005938 cell cortex	IDA PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli...	KEEP AS NON CORE	Summary: LKB1 accumulates at the cell cortex. Reason: LKB1 overexpression leads to cortical accumulation. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epithelial integrity through endosomal LKB1 regulation.
GO:0004674 protein serine/threonine kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: LKB1 is a serine/threonine protein kinase. Reason: UniProt catalytic activity indicates serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
GO:0005938 cell cortex	IDA PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d...	KEEP AS NON CORE	Summary: LKB1 accumulates at the cell cortex. Reason: LKB1 overexpression leads to cortical accumulation. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex
GO:0072697 protein localization to cell cortex	IMP PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d...	KEEP AS NON CORE	Summary: LKB1 localizes to the cell cortex. Reason: LKB1 accumulates at the cell cortex in neuroblasts. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex
GO:0072697 protein localization to cell cortex	IGI PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d...	KEEP AS NON CORE	Summary: LKB1 localizes to the cell cortex. Reason: LKB1 accumulates at the cell cortex in neuroblasts. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex
GO:0045201 maintenance of neuroblast polarity	IDA PMID:22248825 Sgt1 acts via an LKB1/AMPK pathway to establish cortical pol...	KEEP AS NON CORE	Summary: LKB1 supports neuroblast cortical polarity. Reason: LKB1 mutants show apical cortical polarity defects in neuroblasts. Supporting Evidence: PMID:22248825 LKB1, or AMPKα all show similar prophase apical cortical polarity defects
GO:0008340 determination of adult lifespan	IDA PMID:21281604 A gain-of-function screen identifies wdb and lkb1 as lifespa...	KEEP AS NON CORE	Summary: LKB1 overexpression extends lifespan in Drosophila. Reason: Gain-of-function lkb1 overexpression extends lifespan. Supporting Evidence: PMID:21281604 overexpression of the lkb1 gene encoding a serine/threonine kinase, reduced organ size and extended lifespan
GO:0007391 dorsal closure	IMP PMID:16273080 JNK pathway mediates apoptotic cell death induced by tumor s...	UNDECIDED	Summary: Dorsal closure is not explicitly supported by the available abstract evidence. Reason: The cited study discusses epithelial morphogenesis broadly, but not dorsal closure specifically. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis
GO:0043065 positive regulation of apoptotic process	IDA PMID:16273080 JNK pathway mediates apoptotic cell death induced by tumor s...	KEEP AS NON CORE	Summary: LKB1 promotes apoptosis via JNK signaling. Reason: LKB1 induces caspase-dependent apoptosis in Drosophila. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis
GO:0046328 regulation of JNK cascade	IDA PMID:16273080 JNK pathway mediates apoptotic cell death induced by tumor s...	KEEP AS NON CORE	Summary: LKB1 activates the JNK signaling pathway. Reason: The JNK pathway is activated by LKB1 and mediates LKB1-dependent apoptosis. Supporting Evidence: PMID:16273080 the JNK pathway was activated by LKB1 and mediated the LKB1-dependent apoptosis
GO:0030709 border follicle cell delamination	IMP PMID:18976916 PAR-1 kinase regulates epithelial detachment and directional...	UNDECIDED	Summary: Border follicle cell delamination is not supported for LKB1 in the cited abstract. Reason: The referenced study centers on PAR-1, not LKB1; direct evidence for LKB1 in border cell delamination is not accessible. Supporting Evidence: PMID:18976916 PAR-1 directly modulates apical-basal polarity between border cells and epithelial cells to promote detachment
GO:0005634 nucleus	IDA PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation...	KEEP AS NON CORE	Summary: LKB1 can localize to the nucleus per UniProt annotation. Reason: UniProt lists nucleus as a subcellular location. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256\|ARBA:ARBA00004496}. Nucleus PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division.
GO:0005737 cytoplasm	IDA PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation...	KEEP AS NON CORE	Summary: LKB1 localizes to the cytoplasm. Reason: UniProt lists cytoplasmic localization. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256\|ARBA:ARBA00004496}. PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division.
GO:0007052 mitotic spindle organization	IMP PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation...	KEEP AS NON CORE	Summary: LKB1 is required for spindle formation. Reason: Mutations disrupt spindle formation in larval brains. Supporting Evidence: PMID:17507418 mutations disrupt spindle formation, resulting in frequent polyploid cells in larval brains
GO:0055059 asymmetric neuroblast division	IMP PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation...	KEEP AS NON CORE	Summary: LKB1 is required for asymmetric neuroblast division. Reason: Mutations affect asymmetric division of larval neuroblasts. Supporting Evidence: PMID:17507418 dlkb1 mutations affect asymmetric division of larval neuroblasts
GO:0016325 oocyte microtubule cytoskeleton organization	IMP PMID:12540903 A role for Drosophila LKB1 in anterior-posterior axis format...	KEEP AS NON CORE	Summary: LKB1 controls repolarization of the oocyte cytoskeleton. Reason: Lkb1 is required for repolarization of the oocyte cytoskeleton. Supporting Evidence: PMID:12540903 homologue, lkb1, is required for the early A-P polarity of the oocyte

Core Functions

Lkb1 is a serine/threonine kinase (STK11) that activates AMPK family kinases to regulate energy stress responses and polarity.

Molecular Function:

protein serine/threonine kinase activity

Supporting Evidence:

file:genes/DROME/Lkb1/Lkb1-uniprot.txt
RecName: Full=Serine/threonine-protein kinase STK11

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:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:12540903

A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity.

PMID:16273080

JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila.

PMID:17507418

The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division.

PMID:18054329

The GC kinase Fray and Mo25 regulate Drosophila asymmetric divisions.

PMID:18976916

PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells.

PMID:21281604

A gain-of-function screen identifies wdb and lkb1 as lifespan-extending genes in Drosophila.

PMID:22248825

Sgt1 acts via an LKB1/AMPK pathway to establish cortical polarity in larval neuroblasts.

PMID:25996931

Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in Drosophila.

PMID:28767695

Drosophila LKB1 is required for the assembly of the polarized actin structure that allows spermatid individualization.

PMID:29084199

Class III phosphatidylinositol-3-OH kinase controls epithelial integrity through endosomal LKB1 regulation.

PMID:36899949

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

📚 Additional Documentation

Deep Research Falcon

(Lkb1-deep-research-falcon.md)

provider: falcon
model: Edison Scientific Literature
cached: true
start_time: '2026-02-01T16:13:19.693015'
end_time: '2026-02-01T16:13:19.696347'
duration_seconds: 0.0
template_file: templates/gene_research_go_focused.md
template_variables:
organism: DROME
gene_id: Lkb1
gene_symbol: Lkb1
uniprot_accession: Q8T9L5
protein_description: 'RecName: Full=Serine/threonine-protein kinase STK11 {ECO:0000256|ARBA:ARBA00068788};
EC=2.7.11.1 {ECO:0000256|ARBA:ARBA00012513};'
gene_info: Name=Lkb1 {ECO:0000313|EMBL:AAF54972.2, ECO:0000313|FlyBase:FBgn0038167};
Synonyms=anon-EST:Posey135 {ECO:0000313|EMBL:AAF54972.2}, dLKB1 {ECO:0000313|EMBL:AAF54972.2},
dlkb1 {ECO:0000313|EMBL:AAF54972.2}, Dmel\CG9374 {ECO:0000313|EMBL:AAF54972.2},
DmLKB1 {ECO:0000313|EMBL:AAF54972.2}, LKB1 {ECO:0000313|EMBL:AAF54972.2}, lkb1
{ECO:0000313|EMBL:AAF54972.2}, LKB1/PEUTZ JEGHERS KINASE {ECO:0000313|EMBL:AAF54972.2},
PAR-4 {ECO:0000313|EMBL:AAF54972.2}, par-4 {ECO:0000313|EMBL:AAF54972.2}, PAR4
{ECO:0000313|EMBL:AAF54972.2}, Par4 {ECO:0000313|EMBL:AAF54972.2}, STK11 {ECO:0000313|EMBL:AAF54972.2};
ORFNames=CG9374 {ECO:0000313|EMBL:AAL39386.1, ECO:0000313|FlyBase:FBgn0038167},
Dmel_CG9374 {ECO:0000313|EMBL:AAF54972.2};
organism_full: Drosophila melanogaster (Fruit fly).
protein_family: Belongs to the protein kinase superfamily. CAMK Ser/Thr
protein_domains: Kinase-like_dom_sf. (IPR011009); LKB1_c. (IPR039154); Prot_kinase_dom.
(IPR000719); Protein_kinase_ATP_BS. (IPR017441); Ser/Thr_kinase_AS. (IPR008271)
provider_config:
timeout: 600
max_retries: 3
parameters:
allowed_domains: []
temperature: 0.1
citation_count: 19

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: Q8T9L5
Protein Description: RecName: Full=Serine/threonine-protein kinase STK11 {ECO:0000256|ARBA:ARBA00068788}; EC=2.7.11.1 {ECO:0000256|ARBA:ARBA00012513};
Gene Information: Name=Lkb1 {ECO:0000313|EMBL:AAF54972.2, ECO:0000313|FlyBase:FBgn0038167}; Synonyms=anon-EST:Posey135 {ECO:0000313|EMBL:AAF54972.2}, dLKB1 {ECO:0000313|EMBL:AAF54972.2}, dlkb1 {ECO:0000313|EMBL:AAF54972.2}, Dmel\CG9374 {ECO:0000313|EMBL:AAF54972.2}, DmLKB1 {ECO:0000313|EMBL:AAF54972.2}, LKB1 {ECO:0000313|EMBL:AAF54972.2}, lkb1 {ECO:0000313|EMBL:AAF54972.2}, LKB1/PEUTZ JEGHERS KINASE {ECO:0000313|EMBL:AAF54972.2}, PAR-4 {ECO:0000313|EMBL:AAF54972.2}, par-4 {ECO:0000313|EMBL:AAF54972.2}, PAR4 {ECO:0000313|EMBL:AAF54972.2}, Par4 {ECO:0000313|EMBL:AAF54972.2}, STK11 {ECO:0000313|EMBL:AAF54972.2}; ORFNames=CG9374 {ECO:0000313|EMBL:AAL39386.1, ECO:0000313|FlyBase:FBgn0038167}, Dmel_CG9374 {ECO:0000313|EMBL:AAF54972.2};
Organism (full): Drosophila melanogaster (Fruit fly).
Protein Family: Belongs to the protein kinase superfamily. CAMK Ser/Thr
Key Domains: Kinase-like_dom_sf. (IPR011009); LKB1_c. (IPR039154); Prot_kinase_dom. (IPR000719); Protein_kinase_ATP_BS. (IPR017441); Ser/Thr_kinase_AS. (IPR008271)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Lkb1" 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 'Lkb1' 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 Lkb1 (gene ID: Lkb1, UniProt: Q8T9L5) 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: Q8T9L5
Protein Description: RecName: Full=Serine/threonine-protein kinase STK11 {ECO:0000256|ARBA:ARBA00068788}; EC=2.7.11.1 {ECO:0000256|ARBA:ARBA00012513};
Gene Information: Name=Lkb1 {ECO:0000313|EMBL:AAF54972.2, ECO:0000313|FlyBase:FBgn0038167}; Synonyms=anon-EST:Posey135 {ECO:0000313|EMBL:AAF54972.2}, dLKB1 {ECO:0000313|EMBL:AAF54972.2}, dlkb1 {ECO:0000313|EMBL:AAF54972.2}, Dmel\CG9374 {ECO:0000313|EMBL:AAF54972.2}, DmLKB1 {ECO:0000313|EMBL:AAF54972.2}, LKB1 {ECO:0000313|EMBL:AAF54972.2}, lkb1 {ECO:0000313|EMBL:AAF54972.2}, LKB1/PEUTZ JEGHERS KINASE {ECO:0000313|EMBL:AAF54972.2}, PAR-4 {ECO:0000313|EMBL:AAF54972.2}, par-4 {ECO:0000313|EMBL:AAF54972.2}, PAR4 {ECO:0000313|EMBL:AAF54972.2}, Par4 {ECO:0000313|EMBL:AAF54972.2}, STK11 {ECO:0000313|EMBL:AAF54972.2}; ORFNames=CG9374 {ECO:0000313|EMBL:AAL39386.1, ECO:0000313|FlyBase:FBgn0038167}, Dmel_CG9374 {ECO:0000313|EMBL:AAF54972.2};
Organism (full): Drosophila melanogaster (Fruit fly).
Protein Family: Belongs to the protein kinase superfamily. CAMK Ser/Thr
Key Domains: Kinase-like_dom_sf. (IPR011009); LKB1_c. (IPR039154); Prot_kinase_dom. (IPR000719); Protein_kinase_ATP_BS. (IPR017441); Ser/Thr_kinase_AS. (IPR008271)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Lkb1" 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 Lkb1 (gene ID: Lkb1, UniProt: Q8T9L5) 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 overview
We verified the target identity, searched and gathered recent and foundational literature, extracted mechanistic evidence on Drosophila Lkb1 (CG9374; STK11) function, localization, pathways, and recent regulatory updates (2023–2024), and synthesized a structured report with citations, URLs, and dates. Identity checks confirm Drosophila melanogaster Lkb1 (UniProt Q8T9L5) is a serine/threonine kinase in the CAMK-like kinase family with a canonical protein kinase domain, consistent with the literature cited below (2003–2024) (partanen2013breakingtheepithelial pages 4-4, amin2009lkb1regulatespolarity pages 1-1, thiele2016subcellularlocalizationof pages 14-18).

Verification of target identity (mandatory)
- Gene symbol and organism: The literature cited explicitly studies Drosophila melanogaster Lkb1 (also called dLKB1/PAR-4; CG9374), controlling oocyte anterior–posterior (AP) polarity, epithelial polarity, retina remodeling, and neuroblast division (e.g., Amin et al., PNAS, 2009, https://doi.org/10.1073/pnas.0812469106; Partanen et al., Phil. Trans. R. Soc. B, 2013, https://doi.org/10.1098/rstb.2013.0111) (amin2009lkb1regulatespolarity pages 1-1, partanen2013breakingtheepithelial pages 4-4).
- Domains/family: Ser/Thr protein kinase, activates AMPK-family kinases; activation by STRAD/MO25 is conserved; these are consistent with the UniProt domain annotations (Thiele 2016 dissertation, https://doi.org/10.5283/epub.31340; Trelford & Shepherd, Cell Commun. Signal., 2024, https://doi.org/10.1186/s12964-024-01689-5) (thiele2016subcellularlocalizationof pages 14-18, trelford2024lkb1biologyassessing pages 15-16, trelford2024lkb1biologyassessing pages 1-2, trelford2024lkb1biologyassessing pages 2-4).
- No cross-species confusion: Where human STK11 is discussed, it is framed as the ortholog; Drosophila-specific experiments and phenotypes are used throughout (amin2009lkb1regulatespolarity pages 1-1, thiele2016subcellularlocalizationof pages 14-18, partanen2013breakingtheepithelial pages 4-4).

Key concepts and definitions (current understanding)
- Biochemical identity and catalytic activity: Lkb1 is a serine/threonine “master kinase” that phosphorylates and activates AMPK and AMPK-related kinases (including MARK/Par-1, SIK, NUAK), coupling energy sensing to polarity, growth, and cell division (Partanen 2013 review; Amin 2009) (partanen2013breakingtheepithelial pages 4-4, amin2009lkb1regulatespolarity pages 1-1). Lkb1 directly phosphorylates Drosophila Par-1 (reported T408) and AMPK, placing it upstream of polarity and metabolic control modules (Thiele 2016; Amin 2009) (thiele2016subcellularlocalizationof pages 18-21, amin2009lkb1regulatespolarity pages 1-1).
- Activation mechanism: The catalytically active unit is a 1:1:1 LKB1–STRAD–MO25 complex that allosterically activates LKB1 and promotes cytoplasmic/membrane localization; STRAD inhibits nuclear import and engages nuclear export, while MO25 stabilizes STRAD and the complex (Trelford & Shepherd 2024, https://doi.org/10.1186/s12964-024-01689-5; Thiele 2016, https://doi.org/10.5283/epub.31340) (trelford2024lkb1biologyassessing pages 4-5, trelford2024lkb1biologyassessing pages 1-2, trelford2024lkb1biologyassessing pages 2-4, thiele2016subcellularlocalizationof pages 14-18).
- Localization determinants: Lkb1 shuttles between nucleus and cytoplasm; active complexes are predominantly cytosolic/membrane-associated. A C-terminal basic/farnesylation region and phospholipid interactions (e.g., phosphatidic acid) promote membrane recruitment necessary in vivo; an N-terminal NLS mediates import (Thiele 2016; Borkowsky et al., Cells 2023, published Mar 6, 2023: https://doi.org/10.3390/cells12050812) (thiele2016subcellularlocalizationof pages 14-18, thiele2016subcellularlocalizationof pages 21-24, borkowsky2023phosphorylationoflkb1 pages 1-2).

Recent developments and latest research (priority 2023–2024)
- PDK1-dependent regulation (2023): In Drosophila, PDK1 binds Lkb1 via a conserved motif and phosphorylates Lkb1 at T353. This phosphorylation decreases Lkb1 catalytic activity, reduces AMPK activation, alters downstream pS6K, and modulates cell/organ growth. CRISPR knock-in flies expressing phospho-mutant Lkb1 (T353A, T353D) show distinct signaling and growth phenotypes, and molecular dynamics suggest phosphorylation remodels the ATP-binding pocket (Borkowsky et al., Cells, 2023-03-06, https://doi.org/10.3390/cells12050812) (borkowsky2023phosphorylationoflkb1 pages 1-2, borkowsky2023phosphorylationoflkb1 pages 4-5, borkowsky2023phosphorylationoflkb1 pages 7-8).
- Consolidated expert synthesis (2024): A comprehensive review underscores STRAD/MO25-dependent activation, nucleocytoplasmic shuttling, and the breadth of AMPK-family downstreams (including Par-1/MARK) in polarity and metabolism; it also discusses therapeutic implications of modulating LKB1 signaling (Trelford & Shepherd, Cell Commun. Signal., 2024-06, https://doi.org/10.1186/s12964-024-01689-5) (trelford2024lkb1biologyassessing pages 15-16, trelford2024lkb1biologyassessing pages 4-5, trelford2024lkb1biologyassessing pages 1-2, trelford2024lkb1biologyassessing pages 16-17, trelford2024lkb1biologyassessing pages 2-4).
- Hippo/Yorkie cross-talk: In conserved contexts, LKB1 has been identified as an upstream regulator influencing Hippo pathway output (Yorkie/YAP/TAZ), linking polarity/metabolism modules with growth control signaling; this connection is noted in recent synthesis accompanying the 2023 Drosophila study (Borkowsky et al., 2023, https://doi.org/10.3390/cells12050812) (borkowsky2023phosphorylationoflkb1 pages 1-2).

Primary function and substrates in Drosophila
- Enzymatic reaction: Lkb1 transfers phosphate from ATP to Ser/Thr residues on downstream kinases. Direct Drosophila substrates supported in the gathered evidence are AMPK and Par-1/MARK; genetic and biochemical data position Lkb1 upstream of these modules in polarity and metabolic responses (Thiele 2016; Amin 2009) (thiele2016subcellularlocalizationof pages 18-21, amin2009lkb1regulatespolarity pages 1-1).
- Substrate specificity: Within the AMPK-related kinase subfamily, Lkb1 activates multiple kinases (MARK/Par-1, SIK, NUAK), with tissue-specific deployment; in photoreceptors, many remodeling phenotypes are AMPK-independent, implicating other AMPK-family substrates downstream of Lkb1 (Amin 2009) (amin2009lkb1regulatespolarity pages 1-1).

Cellular localization and sites of action
- Oocyte and follicle epithelium: Lkb1 is essential for oocyte AP axis formation and epithelial apico–basal polarity, ensuring proper localization of PAR proteins and adherens junctions (Partanen 2013; Amin 2009) (partanen2013breakingtheepithelial pages 4-4, amin2009lkb1regulatespolarity pages 1-1).
- Pupal retina: During dramatic polarity remodeling, Lkb1 positions adherens junctions and restricts apical domain expansion; AMPK is not the primary mediator in this context (Amin 2009) (amin2009lkb1regulatespolarity pages 1-1).
- Neuroblasts: Lkb1 is required for correct apical polarity complex localization, spindle assembly, and asymmetric division; mutants show spindle defects and polyploidy (Thiele 2016) (thiele2016subcellularlocalizationof pages 18-21).
- Subcellular: Active Lkb1–STRAD–MO25 complexes localize to cytoplasm and cortex/membrane; nuclear export is enhanced by STRAD, while C-terminal motifs that bind acidic lipids and undergo lipid modification promote membrane association (Thiele 2016; Borkowsky 2023) (thiele2016subcellularlocalizationof pages 14-18, thiele2016subcellularlocalizationof pages 21-24, borkowsky2023phosphorylationoflkb1 pages 1-2).

Roles in pathways: polarity, spindle assembly, and metabolism
- Polarity establishment and remodeling: Lkb1 orchestrates polarity in the oocyte (AP axis), follicle epithelium (apico–basal polarity), and pupal retina (AJ placement, apical domain restriction), engaging Par-1/MARK and other AMPK-related kinases in a context-dependent manner (Amin 2009; Partanen 2013) (amin2009lkb1regulatespolarity pages 1-1, partanen2013breakingtheepithelial pages 4-4).
- Spindle assembly/asymmetric division: Lkb1 is necessary for proper spindle formation and neuroblast asymmetric division, acting upstream of Par-1/AMPK modules (Thiele 2016) (thiele2016subcellularlocalizationof pages 18-21).
- Metabolic control: Lkb1→AMPK activation links energy status to mTOR antagonism and autophagy; in Drosophila, PDK1-mediated phosphorylation of Lkb1 reduces AMPK activation and shifts growth signaling (Borkowsky 2023; Trelford & Shepherd 2024) (borkowsky2023phosphorylationoflkb1 pages 7-8, borkowsky2023phosphorylationoflkb1 pages 1-2, trelford2024lkb1biologyassessing pages 4-5).

Interactions with STRAD/MO25 homologs
- STRAD (STE20-like pseudokinase) and MO25 form a heterotrimeric complex with Lkb1 that is essential for allosteric activation and cytoplasmic localization. In Drosophila neuroblasts, STRAD/MO25 co-immunoprecipitate with Lkb1; altering STRAD/MO25 interactions perturbs localization/activity, while PDK1 phosphorylation at T353 does not disrupt STRAD/MO25 binding (Thiele 2016; Borkowsky 2023) (thiele2016subcellularlocalizationof pages 14-18, borkowsky2023phosphorylationoflkb1 pages 7-8).

Current applications and real-world implementations
- Polarity and development models: Drosophila Lkb1 is a tractable in vivo system to dissect polarity establishment (oocyte AP axis, epithelial polarity) and remodeling (pupal retina), enabling genetic tests of AMPK-family downstreams and polarity networks (Amin 2009; Partanen 2013) (amin2009lkb1regulatespolarity pages 1-1, partanen2013breakingtheepithelial pages 4-4).
- Disease relevance and tool development: Human STK11/LKB1 is a tumor suppressor mutated in Peutz–Jeghers syndrome and cancers; the 2024 review outlines therapeutic strategies and the need for LKB1-pathway modulators, emphasizing challenges due to STRAD/MO25 dependency, isoforms, and PTMs (Trelford & Shepherd 2024, https://doi.org/10.1186/s12964-024-01689-5) (trelford2024lkb1biologyassessing pages 15-16, trelford2024lkb1biologyassessing pages 1-2).
- Regulatory axis as a target: The 2023 Drosophila study highlights PDK1→Lkb1 phosphorylation as a conserved regulatory input connecting PI3K-PDK1 signals to LKB1–AMPK growth control, suggesting nodes for pharmacologic intervention or genetic manipulation (Borkowsky 2023, https://doi.org/10.3390/cells12050812) (borkowsky2023phosphorylationoflkb1 pages 1-2, borkowsky2023phosphorylationoflkb1 pages 7-8).

Expert opinions and analysis
- Polarity–metabolism integration: Authoritative reviews emphasize LKB1 as a central integrator of cell polarity and metabolic stress responses, acting through AMPK and AMPK-related kinases, with activation critically dependent on STRAD/MO25 and nucleocytoplasmic shuttling (Partanen 2013; Trelford & Shepherd 2024) (partanen2013breakingtheepithelial pages 4-4, trelford2024lkb1biologyassessing pages 4-5, trelford2024lkb1biologyassessing pages 1-2, trelford2024lkb1biologyassessing pages 2-4).
- Context dependence of downstreams: Eye remodeling phenotypes that are largely AMPK-independent indicate that distinct AMPK-family effectors (e.g., Par-1/MARK, SIK, NUAK) mediate Lkb1 outputs in different tissues, aligning with the “master kinase” paradigm and arguing against single-effector models (Amin 2009) (amin2009lkb1regulatespolarity pages 1-1).
- Upstream regulation: New data place PDK1 as a direct inhibitor of Lkb1 catalytic activity via kinase domain phosphorylation (T353 in fly), refining models of how growth factor/PI3K signals can tune LKB1–AMPK pathway output (Borkowsky 2023) (borkowsky2023phosphorylationoflkb1 pages 7-8, borkowsky2023phosphorylationoflkb1 pages 1-2).

Relevant statistics and data (recent studies)
- PDK1→Lkb1 knock-in phenotypes: MARCM mitotic index (pH3 S10) in wing disc clones: WT ≈1.2%, T353A ≈0.9%, T353D ≈1.4%; adult body-size differences measured (n≥35 per genotype); survival similar across genotypes (n≈100). Biochemical assays show reduced pAMPK and increased pS6K with phospho-mimetic T353D (Borkowsky 2023, 2023-03-06, https://doi.org/10.3390/cells12050812) (borkowsky2023phosphorylationoflkb1 pages 4-5, borkowsky2023phosphorylationoflkb1 pages 7-8).
- Retina polarity remodeling: lkb1 mutant photoreceptors exhibit elongated rhabdomeres and expanded apical/junctional domains with AJ misplacement; AMPK mutants do not replicate these phenotypes under the same conditions, supporting AMPK-independent outputs (Amin 2009, 2009-06-02 online, https://doi.org/10.1073/pnas.0812469106) (amin2009lkb1regulatespolarity pages 1-1, amin2009lkb1regulatespolarity pages 6-6).

Concise evidence table
| Category | Finding (1–2 sentences) | Experimental context | Primary downstream target(s) | Source (year and URL) | Citation ID |
|---|---|---|---|---|---|
| Biochemical function | Lkb1 is a serine/threonine "master" kinase that activates the AMPK-family of kinases and couples energy sensing to polarity and growth control. | Genetic, biochemical, and review syntheses in Drosophila and conserved models. | AMPK-family kinases (AMPK, MARK/Par-1, NUAK, SIK, etc.) | Partanen et al., 2013 (review) https://doi.org/10.1098/rstb.2013.0111; Amin et al., 2009 (PNAS) https://doi.org/10.1073/pnas.0812469106 | (partanen2013breakingtheepithelial pages 4-4, amin2009lkb1regulatespolarity pages 1-1) |
| Direct substrates in flies | Lkb1 phosphorylates and activates AMPK and directly phosphorylates Par-1 (reported Par-1 phosphorylation at T408), linking metabolism to polarity. | In vitro kinase assays, mutant/rescue experiments and biochemical mapping in Drosophila models. | AMPK; PAR-1 (T408) | Thiele, 2016 (dissertation) https://doi.org/10.5283/epub.31340; Amin et al., 2009 https://doi.org/10.1073/pnas.0812469106 | (thiele2016subcellularlocalizationof pages 18-21, amin2009lkb1regulatespolarity pages 1-1) |
| STRAD/Mo25 complex & localization | STRAD and Mo25 binding stabilizes an active Lkb1 conformation and promotes cytoplasmic/membrane localization necessary for functional signaling. | Co-immunoprecipitation, overexpression and rescue assays in neuroblasts and epithelial cells. | STRAD (Strad homolog), Mo25 (adaptor complex) | Thiele, 2016 https://doi.org/10.5283/epub.31340; Partanen et al., 2013 https://doi.org/10.1098/rstb.2013.0111 | (thiele2016subcellularlocalizationof pages 14-18, partanen2013breakingtheepithelial pages 4-4) |
| Oocyte AP axis & epithelial polarity | Lkb1 is required for anterior–posterior axis establishment in the oocyte and for apical–basal polarity in follicle/epithelial cells; loss mislocalizes Par proteins and junctional markers. | Genetic loss-of-function and germline/clonal analyses during oogenesis and follicle/epithelium development. | Par proteins (including Par-1), AMPK (context-dependent) | Partanen et al., 2013 https://doi.org/10.1098/rstb.2013.0111; Amin et al., 2009 https://doi.org/10.1073/pnas.0812469106 | (partanen2013breakingtheepithelial pages 4-4, amin2009lkb1regulatespolarity pages 1-1) |
| Neuroblast spindle & asymmetric division | Lkb1 is necessary for proper spindle formation and asymmetric neuroblast division; mutants show spindle defects, polarity protein mislocalization, and polyploidy. | Larval neuroblast imaging, mutant phenotyping and biochemical assays. | Par-1 and AMPK-family effectors implicated in mediating division/spindle roles | Thiele, 2016 https://doi.org/10.5283/epub.31340; Amin et al., 2009 https://doi.org/10.1073/pnas.0812469106 | (thiele2016subcellularlocalizationof pages 18-21, amin2009lkb1regulatespolarity pages 1-1) |
| Eye/pupal retina polarity remodeling | Lkb1 controls polarity remodeling and adherens junction placement in the pupal retina; many retinal phenotypes are largely AMPK-independent, implying multiple downstream AMPK-like kinases. | MARCM clonal analysis, RNAi and genetic interaction studies in pupal retina. | Multiple AMPK-family kinases (Par-1, SIK, NUAK, etc.) | Amin et al., 2009 (PNAS) https://doi.org/10.1073/pnas.0812469106 | (amin2009lkb1regulatespolarity pages 1-1) |
| 2023: PDK1 phosphorylation regulates Lkb1 | PDK1 binds a conserved motif and phosphorylates Lkb1 at T353 in Drosophila; this phosphorylation reduces Lkb1 activity toward AMPK, altering pAMPK/pS6K and increasing cell/organ size. | In vitro kinase assays, CRISPR knock-in flies (WT, T353A, T353D), MD simulations, signaling blots. | AMPK signaling (reduced pAMPK) and downstream mTOR readouts | Borkowsky et al., 2023 https://doi.org/10.17879/90089628698 | (borkowsky2023phosphorylationoflkb1 pages 1-2, borkowsky2023phosphorylationoflkb1 pages 4-5, borkowsky2023phosphorylationoflkb1 pages 7-8) |
| Quantitative phenotypes / metrics | Reported metrics include MARCM mitotic index (pH3): WT ≈1.2%, T353A ≈0.9%, T353D ≈1.4%; body-size differences measured (n≥35), survival assays (n≈100); retina lkb1 clones show elongated rhabdomeres and AJ defects. | MARCM clone counts, adult body-size measurements, survival assays, pupal retina imaging. | Phenotypic readouts reflecting Lkb1 perturbation (mitotic index, body size, survival, retinal morphology) | Borkowsky et al., 2023 https://doi.org/10.17879/90089628698; Amin et al., 2009 https://doi.org/10.1073/pnas.0812469106 | (borkowsky2023phosphorylationoflkb1 pages 7-8, borkowsky2023phosphorylationoflkb1 pages 4-5, amin2009lkb1regulatespolarity pages 1-1) |

Table: A concise evidence-linked table summarizing biochemical function, substrates, localization control, developmental roles, recent 2023 regulation by PDK1, and quantitative phenotypes for D. melanogaster Lkb1 (UniProt Q8T9L5), with source links and tool-evidence IDs for traceability.

Gene product localization and compartments
- Predominantly cytosolic and membrane-associated when active; nuclear pools exist and are regulated by STRAD-dependent export and importin-dependent import. C-terminal lipidation/phospholipid binding promotes membrane targeting in epithelia and neuroblasts (Thiele 2016; Borkowsky 2023) (thiele2016subcellularlocalizationof pages 21-24, thiele2016subcellularlocalizationof pages 14-18, borkowsky2023phosphorylationoflkb1 pages 1-2).

Scope and limitations of evidence
- Direct phosphorylation of AMPK and Par-1 in Drosophila is supported by biochemical and genetic evidence; however, the relative contributions of other AMPK-related kinases (e.g., SIK, NUAK) remain incompletely quantified in each tissue and stage (Amin 2009; Thiele 2016) (amin2009lkb1regulatespolarity pages 1-1, thiele2016subcellularlocalizationof pages 18-21).
- Hippo/Yorkie cross-talk is indicated in recent synthesis accompanying primary data; dedicated Drosophila in vivo dissection of this axis in 2023–2024 remains to be expanded (Borkowsky 2023) (borkowsky2023phosphorylationoflkb1 pages 1-2).

References with URLs and dates
- Amin et al., Lkb1 regulates polarity remodeling and adherens junction formation in the Drosophila eye. PNAS. Published online 2009-06-02. URL: https://doi.org/10.1073/pnas.0812469106 (amin2009lkb1regulatespolarity pages 1-1, amin2009lkb1regulatespolarity pages 6-6).
- Partanen et al., Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4. Phil. Trans. R. Soc. B. Published 2013-11-05. URL: https://doi.org/10.1098/rstb.2013.0111 (partanen2013breakingtheepithelial pages 4-4).
- Thiele, Subcellular localization of LKB1 and characterization of its interactions with the membrane skeleton in Drosophila melanogaster. Dissertation. 2016-01. URL: https://doi.org/10.5283/epub.31340 (thiele2016subcellularlocalizationof pages 14-18, thiele2016subcellularlocalizationof pages 18-21, thiele2016subcellularlocalizationof pages 21-24).
- Borkowsky et al., Phosphorylation of LKB1 by PDK1 inhibits cell proliferation and organ growth by decreased activation of AMPK. Cells. Published 2023-03-06. URL: https://doi.org/10.3390/cells12050812 (borkowsky2023phosphorylationoflkb1 pages 1-2, borkowsky2023phosphorylationoflkb1 pages 4-5, borkowsky2023phosphorylationoflkb1 pages 7-8).
- Trelford & Shepherd, LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors. Cell Communication and Signaling. Published 2024-06-10. URL: https://doi.org/10.1186/s12964-024-01689-5 (trelford2024lkb1biologyassessing pages 15-16, trelford2024lkb1biologyassessing pages 4-5, trelford2024lkb1biologyassessing pages 1-2, trelford2024lkb1biologyassessing pages 16-17, trelford2024lkb1biologyassessing pages 2-4).

Conclusion
Drosophila Lkb1 (CG9374; STK11) is a conserved master serine/threonine kinase that activates AMPK-family kinases to coordinate polarity, division, and metabolic signaling. In flies, it directly activates AMPK and phosphorylates Par-1/MARK, and its active STRAD/MO25-bound complex localizes to cytoplasm and membranes to execute polarity programs in oocytes, epithelia, retina, and neuroblasts. Recent 2023 work identifies PDK1 as a direct inhibitory regulator of Lkb1 catalytic activity via T353 phosphorylation, linking PI3K–PDK1 cues to Lkb1–AMPK growth control in vivo. These mechanistic insights, together with 2024 synthesis on activation/localization, refine experimental strategies and therapeutic thinking about LKB1-pathway modulation across systems (amin2009lkb1regulatespolarity pages 1-1, thiele2016subcellularlocalizationof pages 18-21, thiele2016subcellularlocalizationof pages 14-18, borkowsky2023phosphorylationoflkb1 pages 1-2, trelford2024lkb1biologyassessing pages 4-5).

References

(partanen2013breakingtheepithelial pages 4-4): Johanna I. Partanen, Topi A. Tervonen, and Juha Klefström. Breaking the epithelial polarity barrier in cancer: the strange case of lkb1/par-4. Philosophical Transactions of the Royal Society B: Biological Sciences, 368:20130111, Nov 2013. URL: https://doi.org/10.1098/rstb.2013.0111, doi:10.1098/rstb.2013.0111. This article has 39 citations and is from a domain leading peer-reviewed journal.
(amin2009lkb1regulatespolarity pages 1-1): Nancy Amin, Afifa Khan, Daniel St. Johnston, Ian Tomlinson, Sophie Martin, Jay Brenman, and Helen McNeill. Lkb1 regulates polarity remodeling and adherens junction formation in the drosophila eye. Proceedings of the National Academy of Sciences, 106:8941-8946, Jun 2009. URL: https://doi.org/10.1073/pnas.0812469106, doi:10.1073/pnas.0812469106. This article has 76 citations and is from a highest quality peer-reviewed journal.
(thiele2016subcellularlocalizationof pages 14-18): Christian Volker Steffen Thiele. Subcellular localization of lkb1 and characterization of its interactions with the membrane skeleton in drosophila melanogaster. Text, Jan 2016. URL: https://doi.org/10.5283/epub.31340, doi:10.5283/epub.31340. This article has 0 citations and is from a peer-reviewed journal.
(trelford2024lkb1biologyassessing pages 15-16): Charles B. Trelford and Trevor G. Shepherd. Lkb1 biology: assessing the therapeutic relevancy of lkb1 inhibitors. Cell Communication and Signaling : CCS, Jun 2024. URL: https://doi.org/10.1186/s12964-024-01689-5, doi:10.1186/s12964-024-01689-5. This article has 22 citations.
(trelford2024lkb1biologyassessing pages 1-2): Charles B. Trelford and Trevor G. Shepherd. Lkb1 biology: assessing the therapeutic relevancy of lkb1 inhibitors. Cell Communication and Signaling : CCS, Jun 2024. URL: https://doi.org/10.1186/s12964-024-01689-5, doi:10.1186/s12964-024-01689-5. This article has 22 citations.
(trelford2024lkb1biologyassessing pages 2-4): Charles B. Trelford and Trevor G. Shepherd. Lkb1 biology: assessing the therapeutic relevancy of lkb1 inhibitors. Cell Communication and Signaling : CCS, Jun 2024. URL: https://doi.org/10.1186/s12964-024-01689-5, doi:10.1186/s12964-024-01689-5. This article has 22 citations.
(thiele2016subcellularlocalizationof pages 18-21): Christian Volker Steffen Thiele. Subcellular localization of lkb1 and characterization of its interactions with the membrane skeleton in drosophila melanogaster. Text, Jan 2016. URL: https://doi.org/10.5283/epub.31340, doi:10.5283/epub.31340. This article has 0 citations and is from a peer-reviewed journal.
(trelford2024lkb1biologyassessing pages 4-5): Charles B. Trelford and Trevor G. Shepherd. Lkb1 biology: assessing the therapeutic relevancy of lkb1 inhibitors. Cell Communication and Signaling : CCS, Jun 2024. URL: https://doi.org/10.1186/s12964-024-01689-5, doi:10.1186/s12964-024-01689-5. This article has 22 citations.
(thiele2016subcellularlocalizationof pages 21-24): Christian Volker Steffen Thiele. Subcellular localization of lkb1 and characterization of its interactions with the membrane skeleton in drosophila melanogaster. Text, Jan 2016. URL: https://doi.org/10.5283/epub.31340, doi:10.5283/epub.31340. This article has 0 citations and is from a peer-reviewed journal.
(borkowsky2023phosphorylationoflkb1 pages 1-2): S Borkowsky, M Gass, A Alavizargar, and J Hanewinkel. Phosphorylation of lkb1 by pdk1 inhibits cell proliferation and organ growth by decreased activation of ampk. cells 2023; 12: 812. Unknown journal, 2023.
(borkowsky2023phosphorylationoflkb1 pages 4-5): S Borkowsky, M Gass, A Alavizargar, and J Hanewinkel. Phosphorylation of lkb1 by pdk1 inhibits cell proliferation and organ growth by decreased activation of ampk. cells 2023; 12: 812. Unknown journal, 2023.
(borkowsky2023phosphorylationoflkb1 pages 7-8): S Borkowsky, M Gass, A Alavizargar, and J Hanewinkel. Phosphorylation of lkb1 by pdk1 inhibits cell proliferation and organ growth by decreased activation of ampk. cells 2023; 12: 812. Unknown journal, 2023.
(trelford2024lkb1biologyassessing pages 16-17): Charles B. Trelford and Trevor G. Shepherd. Lkb1 biology: assessing the therapeutic relevancy of lkb1 inhibitors. Cell Communication and Signaling : CCS, Jun 2024. URL: https://doi.org/10.1186/s12964-024-01689-5, doi:10.1186/s12964-024-01689-5. This article has 22 citations.
(amin2009lkb1regulatespolarity pages 6-6): Nancy Amin, Afifa Khan, Daniel St. Johnston, Ian Tomlinson, Sophie Martin, Jay Brenman, and Helen McNeill. Lkb1 regulates polarity remodeling and adherens junction formation in the drosophila eye. Proceedings of the National Academy of Sciences, 106:8941-8946, Jun 2009. URL: https://doi.org/10.1073/pnas.0812469106, doi:10.1073/pnas.0812469106. This article has 76 citations and is from a highest quality peer-reviewed journal.

Citations

thiele2016subcellularlocalizationof pages 18-21
partanen2013breakingtheepithelial pages 4-4
thiele2016subcellularlocalizationof pages 14-18
thiele2016subcellularlocalizationof pages 21-24
https://doi.org/10.1073/pnas.0812469106;
https://doi.org/10.1098/rstb.2013.0111
https://doi.org/10.5283/epub.31340;
https://doi.org/10.1186/s12964-024-01689-5
https://doi.org/10.1186/s12964-024-01689-5;
https://doi.org/10.5283/epub.31340
https://doi.org/10.3390/cells12050812
https://doi.org/10.1073/pnas.0812469106
https://doi.org/10.1098/rstb.2013.0111;
https://doi.org/10.17879/90089628698
https://doi.org/10.17879/90089628698;
https://doi.org/10.1098/rstb.2013.0111,
https://doi.org/10.1073/pnas.0812469106,
https://doi.org/10.5283/epub.31340,
https://doi.org/10.1186/s12964-024-01689-5,

📄 View Raw YAML

id: Q8T9L5
gene_symbol: Lkb1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: 'Serine/threonine kinase STK11 that activates AMPK-family kinases and
  regulates polarity, growth, and energy stress responses.'
existing_annotations:
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: LKB1 is a serine/threonine protein kinase.
    action: ACCEPT
    reason: UniProt catalytic activity indicates serine/threonine kinase 
      function.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
    - reference_id: file:genes/DROME/Lkb1/Lkb1-deep-research-falcon.md
      supporting_text: 'RecName: Full=Serine/threonine-protein kinase STK11'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review: &id001
    summary: LKB1 localizes to the cytoplasm.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists cytoplasmic localization.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.'
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: LKB1 participates in intracellular signal transduction via 
      AMPK-related kinases.
    action: KEEP_AS_NON_CORE
    reason: Regulation of AMPK-family kinases places LKB1 in intracellular 
      signaling pathways.
    supported_by:
    - reference_id: PMID:25996931
      supporting_text: LKB1 plays important roles in governing energy 
        homeostasis by regulating AMP-activated protein kinase (AMPK) and other 
        AMPK-related kinases
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: LKB1 binds nucleotides as part of its kinase reaction.
    action: KEEP_AS_NON_CORE
    reason: The catalytic reaction uses ATP, indicating nucleotide binding.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0001558
    label: regulation of cell growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: LKB1 regulates organ growth through apoptosis signaling.
    action: KEEP_AS_NON_CORE
    reason: LKB1 negatively regulates organ growth via apoptosis.
    supported_by:
    - reference_id: PMID:16273080
      supporting_text: Drosophila LKB1 negatively regulates organ growth by 
        caspase-dependent apoptosis
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: LKB1 has protein kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Catalytic activity confirms protein kinase function.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review: &id002
    summary: LKB1 is a serine/threonine protein kinase.
    action: ACCEPT
    reason: UniProt catalytic activity indicates serine/threonine kinase 
      function.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: LKB1 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/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: LKB1 can localize to the nucleus per UniProt annotation.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists nucleus as a subcellular location.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.
        Nucleus'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review: *id001
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: LKB1 regulates apoptosis rather than being a core apoptotic 
      machinery component.
    action: MODIFY
    reason: LKB1 induces apoptosis via JNK signaling; use positive regulation of
      apoptotic process.
    proposed_replacement_terms:
    - id: GO:0043065
      label: positive regulation of apoptotic process
    supported_by:
    - reference_id: PMID:16273080
      supporting_text: Drosophila LKB1 negatively regulates organ growth by 
        caspase-dependent apoptosis
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: DNA damage response is not supported by the accessible sources.
    action: UNDECIDED
    reason: No direct DNA damage response evidence was found in the available 
      abstracts.
    supported_by:
    - reference_id: PMID:17507418
      supporting_text: mutations disrupt spindle formation, resulting in 
        frequent polyploid cells in larval brains
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: LKB1 has kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Catalytic activity confirms kinase function.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: LKB1 is a transferase (kinase) enzyme.
    action: KEEP_AS_NON_CORE
    reason: Kinases transfer phosphate groups from ATP.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
- term:
    id: GO:0030010
    label: establishment of cell polarity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: LKB1 is required for cell polarity establishment.
    action: KEEP_AS_NON_CORE
    reason: Lkb1 is required for oocyte A-P polarity and epithelial polarity.
    supported_by:
    - reference_id: PMID:12540903
      supporting_text: homologue, lkb1, is required for the early A-P polarity 
        of the oocyte
- term:
    id: GO:0030295
    label: protein kinase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: LKB1 activates AMPK and related kinases.
    action: KEEP_AS_NON_CORE
    reason: LKB1 regulates AMPK and other AMPK-related kinases.
    supported_by:
    - reference_id: PMID:25996931
      supporting_text: LKB1 plays important roles in governing energy 
        homeostasis by regulating AMP-activated protein kinase (AMPK) and other 
        AMPK-related kinases
- term:
    id: GO:0042593
    label: glucose homeostasis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Glucose homeostasis is not directly supported by the accessible 
      evidence.
    action: UNDECIDED
    reason: Available sources focus on lipid metabolism and polarity rather than
      glucose homeostasis.
    supported_by:
    - reference_id: PMID:25996931
      supporting_text: LKB1 mutants display decreased lipid storage and 
        increased gene expression of brummer
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: LKB1 binds divalent metal ions required for catalysis.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Mg2+ and Mn2+ as cofactors.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: Name=Mg(2+)
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: Name=Mn(2+)
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:36899949
  review:
    summary: Positive regulation of cell proliferation is not supported for 
      LKB1.
    action: MARK_AS_OVER_ANNOTATED
    reason: LKB1 acts as a tumor suppressor and restricts growth; the cited 
      study links LKB1 inhibition to increased growth.
    supported_by:
    - reference_id: PMID:16273080
      supporting_text: Drosophila LKB1 negatively regulates organ growth by 
        caspase-dependent apoptosis
    - 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: IDA
  original_reference_id: PMID:36899949
  review:
    summary: LKB1 association with membranes is noted in the PDK1 interaction 
      study.
    action: KEEP_AS_NON_CORE
    reason: PDK1-mediated regulation of LKB1 involves membrane-associated 
      interactions.
    supported_by:
    - reference_id: PMID:36899949
      supporting_text: phosphorylation of LKB1 by PDK1 results in an inhibition 
        of LKB1, decreased activation of AMPK and enhanced cell growth
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IDA
  original_reference_id: PMID:36899949
  review:
    summary: LKB1 activates serine/threonine kinases such as AMPK/SIKs.
    action: KEEP_AS_NON_CORE
    reason: LKB1 regulates AMPK and other AMPK-related kinases.
    supported_by:
    - reference_id: PMID:25996931
      supporting_text: LKB1 plays important roles in governing energy 
        homeostasis by regulating AMP-activated protein kinase (AMPK) and other 
        AMPK-related kinases
    - 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:1904263
    label: positive regulation of TORC1 signaling
  evidence_type: IMP
  original_reference_id: PMID:36899949
  review:
    summary: Positive regulation of TORC1 signaling is inconsistent with 
      LKB1–AMPK inhibition of mTOR.
    action: MODIFY
    reason: AMPK activation downstream of LKB1 inhibits mTOR; use negative 
      regulation of TORC1 signaling instead.
    proposed_replacement_terms:
    - id: GO:1904262
      label: negative regulation of TORC1 signaling
    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:0007291
    label: sperm individualization
  evidence_type: IMP
  original_reference_id: PMID:28767695
  review:
    summary: LKB1 is required for spermatid individualization.
    action: KEEP_AS_NON_CORE
    reason: LKB1 is required for actin cone formation enabling spermatid 
      individualization.
    supported_by:
    - reference_id: PMID:28767695
      supporting_text: dLKB1 is required in the germline for the formation of 
        the actin cone, the polarized structure that allows spermatid 
        individualization
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:25996931
  review:
    summary: LKB1 is a serine/threonine protein kinase.
    action: ACCEPT
    reason: UniProt catalytic activity indicates serine/threonine kinase 
      function.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + 
        ADP + H(+)
    - reference_id: PMID:25996931
      supporting_text: Feeding and Fasting Signals Converge on the LKB1-SIK3 
        Pathway to Regulate Lipid Metabolism in Drosophila.
- term:
    id: GO:0010897
    label: negative regulation of triglyceride catabolic process
  evidence_type: IMP
  original_reference_id: PMID:25996931
  review:
    summary: LKB1 suppresses lipolysis and supports lipid storage.
    action: KEEP_AS_NON_CORE
    reason: LKB1 mutants show decreased lipid storage and increased lipase 
      expression.
    supported_by:
    - reference_id: PMID:25996931
      supporting_text: LKB1 mutants display decreased lipid storage and 
        increased gene expression of brummer
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29084199
  review:
    summary: Protein binding evidence is not explicit in the available abstract 
      for this annotation.
    action: UNDECIDED
    reason: The endosomal regulation study does not explicitly document LKB1 
      binding partners in the abstract.
    supported_by:
    - reference_id: PMID:29084199
      supporting_text: dysregulation of endosomally localized Liver Kinase B1 
        (LKB1, also known as STK11)
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:29084199
  review:
    summary: LKB1 localizes to endosomes in epithelial cells.
    action: KEEP_AS_NON_CORE
    reason: Endosomal LKB1 localization is reported in epithelial integrity 
      studies.
    supported_by:
    - reference_id: PMID:29084199
      supporting_text: dysregulation of endosomally localized Liver Kinase B1 
        (LKB1, also known as STK11)
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: IDA
  original_reference_id: PMID:29084199
  review:
    summary: LKB1 accumulates at the cell cortex.
    action: KEEP_AS_NON_CORE
    reason: LKB1 overexpression leads to cortical accumulation.
    supported_by:
    - reference_id: PMID:18054329
      supporting_text: Lkb1, which accumulates in the cell cortex
    - reference_id: PMID:29084199
      supporting_text: Class III phosphatidylinositol-3-OH kinase controls 
        epithelial integrity through endosomal LKB1 regulation.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review: *id002
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: IDA
  original_reference_id: PMID:18054329
  review:
    summary: LKB1 accumulates at the cell cortex.
    action: KEEP_AS_NON_CORE
    reason: LKB1 overexpression leads to cortical accumulation.
    supported_by:
    - reference_id: PMID:18054329
      supporting_text: Lkb1, which accumulates in the cell cortex
- term:
    id: GO:0072697
    label: protein localization to cell cortex
  evidence_type: IMP
  original_reference_id: PMID:18054329
  review: &id003
    summary: LKB1 localizes to the cell cortex.
    action: KEEP_AS_NON_CORE
    reason: LKB1 accumulates at the cell cortex in neuroblasts.
    supported_by:
    - reference_id: PMID:18054329
      supporting_text: Lkb1, which accumulates in the cell cortex
- term:
    id: GO:0072697
    label: protein localization to cell cortex
  evidence_type: IGI
  original_reference_id: PMID:18054329
  review: *id003
- term:
    id: GO:0045201
    label: maintenance of neuroblast polarity
  evidence_type: IDA
  original_reference_id: PMID:22248825
  review:
    summary: LKB1 supports neuroblast cortical polarity.
    action: KEEP_AS_NON_CORE
    reason: LKB1 mutants show apical cortical polarity defects in neuroblasts.
    supported_by:
    - reference_id: PMID:22248825
      supporting_text: LKB1, or AMPKα all show similar prophase apical cortical 
        polarity defects
- term:
    id: GO:0008340
    label: determination of adult lifespan
  evidence_type: IDA
  original_reference_id: PMID:21281604
  review:
    summary: LKB1 overexpression extends lifespan in Drosophila.
    action: KEEP_AS_NON_CORE
    reason: Gain-of-function lkb1 overexpression extends lifespan.
    supported_by:
    - reference_id: PMID:21281604
      supporting_text: overexpression of the lkb1 gene encoding a 
        serine/threonine kinase, reduced organ size and extended lifespan
- term:
    id: GO:0007391
    label: dorsal closure
  evidence_type: IMP
  original_reference_id: PMID:16273080
  review:
    summary: Dorsal closure is not explicitly supported by the available 
      abstract evidence.
    action: UNDECIDED
    reason: The cited study discusses epithelial morphogenesis broadly, but not 
      dorsal closure specifically.
    supported_by:
    - reference_id: PMID:16273080
      supporting_text: Drosophila LKB1 negatively regulates organ growth by 
        caspase-dependent apoptosis
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:16273080
  review:
    summary: LKB1 promotes apoptosis via JNK signaling.
    action: KEEP_AS_NON_CORE
    reason: LKB1 induces caspase-dependent apoptosis in Drosophila.
    supported_by:
    - reference_id: PMID:16273080
      supporting_text: Drosophila LKB1 negatively regulates organ growth by 
        caspase-dependent apoptosis
- term:
    id: GO:0046328
    label: regulation of JNK cascade
  evidence_type: IDA
  original_reference_id: PMID:16273080
  review:
    summary: LKB1 activates the JNK signaling pathway.
    action: KEEP_AS_NON_CORE
    reason: The JNK pathway is activated by LKB1 and mediates LKB1-dependent 
      apoptosis.
    supported_by:
    - reference_id: PMID:16273080
      supporting_text: the JNK pathway was activated by LKB1 and mediated the 
        LKB1-dependent apoptosis
- term:
    id: GO:0030709
    label: border follicle cell delamination
  evidence_type: IMP
  original_reference_id: PMID:18976916
  review:
    summary: Border follicle cell delamination is not supported for LKB1 in the 
      cited abstract.
    action: UNDECIDED
    reason: The referenced study centers on PAR-1, not LKB1; direct evidence for
      LKB1 in border cell delamination is not accessible.
    supported_by:
    - reference_id: PMID:18976916
      supporting_text: PAR-1 directly modulates apical-basal polarity between 
        border cells and epithelial cells to promote detachment
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17507418
  review:
    summary: LKB1 can localize to the nucleus per UniProt annotation.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists nucleus as a subcellular location.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.
        Nucleus'
    - reference_id: PMID:17507418
      supporting_text: The Drosophila Lkb1 kinase is required for spindle 
        formation and asymmetric neuroblast division.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17507418
  review:
    summary: LKB1 localizes to the cytoplasm.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists cytoplasmic localization.
    supported_by:
    - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.'
    - reference_id: PMID:17507418
      supporting_text: The Drosophila Lkb1 kinase is required for spindle 
        formation and asymmetric neuroblast division.
- term:
    id: GO:0007052
    label: mitotic spindle organization
  evidence_type: IMP
  original_reference_id: PMID:17507418
  review:
    summary: LKB1 is required for spindle formation.
    action: KEEP_AS_NON_CORE
    reason: Mutations disrupt spindle formation in larval brains.
    supported_by:
    - reference_id: PMID:17507418
      supporting_text: mutations disrupt spindle formation, resulting in 
        frequent polyploid cells in larval brains
- term:
    id: GO:0055059
    label: asymmetric neuroblast division
  evidence_type: IMP
  original_reference_id: PMID:17507418
  review:
    summary: LKB1 is required for asymmetric neuroblast division.
    action: KEEP_AS_NON_CORE
    reason: Mutations affect asymmetric division of larval neuroblasts.
    supported_by:
    - reference_id: PMID:17507418
      supporting_text: dlkb1 mutations affect asymmetric division of larval 
        neuroblasts
- term:
    id: GO:0016325
    label: oocyte microtubule cytoskeleton organization
  evidence_type: IMP
  original_reference_id: PMID:12540903
  review:
    summary: LKB1 controls repolarization of the oocyte cytoskeleton.
    action: KEEP_AS_NON_CORE
    reason: Lkb1 is required for repolarization of the oocyte cytoskeleton.
    supported_by:
    - reference_id: PMID:12540903
      supporting_text: homologue, lkb1, is required for the early A-P polarity 
        of the oocyte
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:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12540903
  title: A role for Drosophila LKB1 in anterior-posterior axis formation and 
    epithelial polarity.
  findings: []
- id: PMID:16273080
  title: JNK pathway mediates apoptotic cell death induced by tumor suppressor 
    LKB1 in Drosophila.
  findings: []
- id: PMID:17507418
  title: The Drosophila Lkb1 kinase is required for spindle formation and 
    asymmetric neuroblast division.
  findings: []
- id: PMID:18054329
  title: The GC kinase Fray and Mo25 regulate Drosophila asymmetric divisions.
  findings: []
- id: PMID:18976916
  title: PAR-1 kinase regulates epithelial detachment and directional protrusion
    of migrating border cells.
  findings: []
- id: PMID:21281604
  title: A gain-of-function screen identifies wdb and lkb1 as lifespan-extending
    genes in Drosophila.
  findings: []
- id: PMID:22248825
  title: Sgt1 acts via an LKB1/AMPK pathway to establish cortical polarity in 
    larval neuroblasts.
  findings: []
- id: PMID:25996931
  title: Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to 
    Regulate Lipid Metabolism in Drosophila.
  findings: []
- id: PMID:28767695
  title: Drosophila LKB1 is required for the assembly of the polarized actin 
    structure that allows spermatid individualization.
  findings: []
- id: PMID:29084199
  title: Class III phosphatidylinositol-3-OH kinase controls epithelial 
    integrity through endosomal LKB1 regulation.
  findings: []
- id: PMID:36899949
  title: Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ 
    Growth by Decreased Activation of AMPK.
  findings: []
core_functions:
- description: Lkb1 is a serine/threonine kinase (STK11) that activates AMPK 
    family kinases to regulate energy stress responses and polarity.
  supported_by:
  - reference_id: file:genes/DROME/Lkb1/Lkb1-uniprot.txt
    supporting_text: 'RecName: Full=Serine/threonine-protein kinase STK11'
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity

Lkb1

Gene Description

Existing Annotations Review

Core Functions

Lkb1 is a serine/threonine kinase (STK11) that activates AMPK family kinases to regulate energy stress responses and polarity.

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