STK11 - Serine/threonine-protein kinase STK11 - human protein (Function)
 
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STK11 »  Serine/threonine-protein kinase STK11   [ EC 2.7.11.1 ]
 
Protein also known as:  Renal carcinoma antigen NY-REN-19.
Gene name:  STK11
Entry whose protein(s) existence is based on evidence at protein level
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1 262 2
GENE REF ISO

Function

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Overview 
Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro).  
8
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
LRR domain bindingdefinition[GO:0030275] silver  
  • IEAOrtholog Compara
Magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAUniProtKB
P53 bindingdefinition[GO:0002039]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
9
  • IPIIntAct
  • IPIBHF-UCL
Protein complex bindingdefinition[GO:0032403] silver  
  • IEAOrtholog Compara
Protein kinase activator activitydefinition[GO:0030295]  
1
  • IDAUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
3
  • IDAUniProtKB
GO biological process 
Activation of protein kinase activitydefinition[GO:0032147]  
1
  • IDAMGI
  • IEAOrtholog Compara
Anoikisdefinition[GO:0043276]  
1
  • IMPBHF-UCL
Autophagydefinition[GO:0006914]  
  • IEAUniProtKB KW
Axonogenesisdefinition[GO:0007409] silver  
  • IEAOrtholog Compara
Canonical Wnt signaling pathwaydefinition[GO:0060070] silver  
  • IEAOrtholog Compara
Cell cycle arrestdefinition[GO:0007050]  
2
  • IDAUniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
  • IEAUniProtKB KW
Establishment of cell polaritydefinition[GO:0030010]  
  • ISSOrtholog Curator
Glucose homeostasisdefinition[GO:0042593]  
  • ISSOrtholog Curator
Golgi localizationdefinition[GO:0051645] silver  
  • IEAOrtholog Compara
Intrinsic apoptotic signaling pathway by p53 class mediatordefinition[GO:0072332]  
1
  • IDAUniProtKB
Negative regulation of cell growthdefinition[GO:0030308]  
  • ISSOrtholog Curator
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • IMPUniProtKB
Negative regulation of epithelial cell proliferation involved in prostate gland developmentdefinition[GO:0060770] silver  
  • IEAOrtholog Compara
Positive regulation of axonogenesisdefinition[GO:0050772] silver  
  • IEAOrtholog Compara
Positive regulation of gluconeogenesisdefinition[GO:0045722] silver  
  • IEAOrtholog Compara
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731] silver  
  • IEAOrtholog Compara
Positive regulation of transforming growth factor beta receptor signaling pathwaydefinition[GO:0030511]  
1
  • IMPBHF-UCL
Positive thymic T cell selectiondefinition[GO:0045059] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Protein heterooligomerizationdefinition[GO:0051291] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of cell growthdefinition[GO:0001558]  
  • ISSOrtholog Curator
Regulation of protein kinase B signalingdefinition[GO:0051896] silver  
  • IEAOrtholog Compara
Regulation of Wnt signaling pathwaydefinition[GO:0030111] silver  
  • IEAOrtholog Compara
Response to glucagondefinition[GO:0033762] silver  
  • IEAOrtholog Compara
Response to ionizing radiationdefinition[GO:0010212]  
  • ISSOrtholog Curator
Response to lipiddefinition[GO:0033993] silver  
  • IEAOrtholog Compara
Spermatid developmentdefinition[GO:0007286] silver  
  • IEAOrtholog Compara
T cell receptor signaling pathwaydefinition[GO:0050852] silver  
  • IEAOrtholog Compara
TCR signalosome assemblydefinition[GO:0036399] silver  
  • IEAOrtholog Compara
Tissue homeostasisdefinition[GO:0001894] silver  
  • IEAOrtholog Compara
Vasculature developmentdefinition[GO:0001944]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • CuratedUniProtKB
It requires the following cofactor
Magnesium or Manganese.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK.  
2
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adipocytokine signaling pathway  hsa04920+6794  
mTOR signaling pathway  hsa04150+6794  
According to Reactome, this protein belongs to the following pathways:
AMPK inhibits chREBP transcriptional activation activity  REACT_1988  
Regulation of AMPK activity via LKB1  REACT_21285  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Autophagy  definition   [KW-0072]
Cell cycle  definition   [KW-0131]
DNA damage  definition   [KW-0227]
Differentiation  definition   [KW-0221]
Spermatogenesis  definition   [KW-0744]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: STK11
GenomeRNAi: 6794
PRO: PR:Q15831
Chemistry
GuidetoPHARMACOLOGY: 2212