Serine/threonine-protein kinase STK11

UniProt Q15831 Organism Homo sapiens Gene LKB1, PJS, STK11 EC 2.7.11.1

Also known as: LKB1, PJS, STK11

Function

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. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: Kinase-like_dom_sf, LKB1_c, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: S-Adenosylmethionine Synthases & related

Experimental structures · PDB · 4

2WTK X-ray 2.65A
4ZDR X-ray 2.90A
5WXN X-ray 2.93A
8VSU EM 2.86A

A predicted model is available from AlphaFold.

Gene Ontology · 45

Disease associations

Peutz-Jeghers syndrome MONDO:0008280
testicular germ cell tumor MONDO:0010108

Neighborhood · nearest proteins

Nearest neighbours of Serine/threonine-protein kinase STK11: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

STE20-related kinase adapter protein alpha 3 shared papers
Nischarin 1 shared papers
Serine/threonine-protein kinase STK11 3 shared papers
tRNA (34-2'-O)-methyltransferase regulator WDR6 1 shared papers
Protein kinase C zeta type 2 shared papers
Nuclear receptor subfamily 4immunitygroup A member 1 1 shared papers
STE20-related kinase adapter protein beta 1 shared papers
Calcium-binding protein 39 1 shared papers
Serine/threonine-protein kinase 11-interacting protein 1 shared papers
Serine/threonine-protein kinase 11-interacting protein 1 shared papers
Serine/threonine-protein kinase NIM1 1 shared papers
NUAK family SNF1-like kinase 1 3 shared papers

Literature · 57 cited papers

Withdrawal: Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J. Biol. Chem. · 2019
A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating CDKN1A (p21WAF1/CIP1) degradation. PLoS Genet. · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Phosphorylation of serine 399 in LKB1 protein short form by protein kinase Czeta is required for its nucleocytoplasmic transport and consequent AMP-activated protein kinase (AMPK) activation. J. Biol. Chem. · 2013
Integrin-binding protein nischarin interacts with tumor suppressor liver kinase B1 (LKB1) to regulate cell migration of breast epithelial cells. J. Biol. Chem. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nat. Chem. Biol. · 2012
A novel de novo mutation in LKB1 gene in a Chinese Peutz Jeghers syndrome patient significantly diminished p53 activity. Clin. Res. Hepatol. Gastroenterol. · 2011
The role of LKB1 and AMPK in cellular responses to stress and damage. FEBS Lett. · 2011
LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor. Protein Cell · 2011
A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation. Oncogene · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
… and 45 more in the literature graph

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