Lkb1

UniProt ID: Q8T9L5
Organism: Drosophila melanogaster
Review Status: INITIALIZED
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Gene Description

Serine/threonine kinase STK11 that activates AMPK-family kinases and regulates polarity, growth, and energy stress responses.

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.
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.
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 AMPKΞ± 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.

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

References

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Deep Research

Falcon

(Lkb1-deep-research-falcon.md)

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