Serine/Threonine Kinase 11 (STK11)

LKB1; PJS; Polarization-Related Protein LKB1; Peutz-Jeghers Syndrome; Liver kinase B1; Renal carcinoma antigen NY-REN-19

SPN	P628
HGNC	11389
MGI	1341870
PubMed	22698401
RGD	1308653
UniProt	Q15831
Wiki	STK11

LKB1 is a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK), a necessary element in cell metabolism that is required for maintaining energy homeostasis. It is now clear that LKB1 exerts its growth suppressing effects by activating a group of other ~14 kinases, comprising AMPK and AMPK-related kinases. Activation of AMPK by LKB1 suppresses growth and proliferation when energy and nutrient levels are scarce. Activation of AMPK-related kinases by LKB1 plays vital roles maintaining cell polarity thereby inhibiting inappropriate expansion of tumour cells. A picture from current research is emerging that loss of LKB1 leads to disorganization of cell polarity and facilitates tumour growth under energetically unfavorable conditions.

Reference

"Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase."
Nat. Genet. 18:38-43(1998) [PubMed] [Europe PMC] [Abstract]

"Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer."
Cancer Res. 58:1384-1386(1998) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and biology of human chromosome 19."
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Antigens recognized by autologous antibody in patients with renal-cell carcinoma."
Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract]

"Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain."
J. Neurooncol. 49:187-195(2000) [PubMed] [Europe PMC] [Abstract]

"LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1."
Hum. Mol. Genet. 10:2869-2877(2001) [PubMed] [Europe PMC] [Abstract]

"The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death."
Mol. Cell 7:1307-1319(2001) [PubMed] [Europe PMC] [Abstract]

"Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung."
Cancer Res. 62:3659-3662(2002) [PubMed] [Europe PMC] [Abstract]

"Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD."
EMBO J. 22:3062-3072(2003) [PubMed] [Europe PMC] [Abstract]

"MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm."
EMBO J. 22:5102-5114(2003) [PubMed] [Europe PMC] [Abstract]

"Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD."
Cell 116:457-466(2004) [PubMed] [Europe PMC] [Abstract]

"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract]

"Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene."
Oncogene 23:4037-4040(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate."
FEBS Lett. 579:1417-1423(2005) [PubMed] [Europe PMC] [Abstract]

"LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes."
Hum. Mol. Genet. 14:2209-2219(2005) [PubMed] [Europe PMC] [Abstract]

"LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation."
Cancer Res. 66:10701-10708(2006) [PubMed] [Europe PMC] [Abstract]

"Association of LKB1 with a WD-repeat protein WDR6 is implicated in cell growth arrest and p27(Kip1) induction."
Mol. Cell. Biochem. 301:115-122(2007) [PubMed] [Europe PMC] [Abstract]

"LKB1 gene mutations in Japanese lung cancer patients."
Cancer Sci. 98:1747-1751(2007) [PubMed] [Europe PMC] [Abstract]

"LKB1 modulates lung cancer differentiation and metastasis."
Nature 448:807-810(2007) [PubMed] [Europe PMC] [Abstract]

"Prevalence and specificity of LKB1 genetic alterations in lung cancers."
Oncogene 26:5911-5918(2007) [PubMed] [Europe PMC] [Abstract]

"Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients."
Br. J. Cancer 99:245-252(2008) [PubMed] [Europe PMC] [Abstract]

"Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells."
J. Biol. Chem. 283:12446-12455(2008) [PubMed] [Europe PMC] [Abstract]

"SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation."
J. Biol. Chem. 283:27628-27635(2008) [PubMed] [Europe PMC] [Abstract]

"Characterization of an alternative splice variant of LKB1."
J. Biol. Chem. 284:67-76(2009) [PubMed] [Europe PMC] [Abstract]

"Large-scale proteomics analysis of the human kinome."
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]

"Spectrum of LKB1, EGFR, and KRAS mutations in Chinese lung adenocarcinomas."
J. Thorac. Oncol. 5:1130-1135(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation."
Oncogene 30:2933-2942(2011) [PubMed] [Europe PMC] [Abstract]

"The role of LKB1 and AMPK in cellular responses to stress and damage."
FEBS Lett. 585:952-957(2011) [PubMed] [Europe PMC] [Abstract]

"LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor."
Protein Cell 2:99-107(2011) [PubMed] [Europe PMC] [Abstract]

"The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK."
Nat. Chem. Biol. 8:897-904(2012) [PubMed] [Europe PMC] [Abstract]

"Integrin-binding protein nischarin interacts with tumor suppressor liver kinase B1 (LKB1) to regulate cell migration of breast epithelial cells."
J. Biol. Chem. 288:15495-15509(2013) [PubMed] [Europe PMC] [Abstract]

"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. 288:16495-16505(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating CDKN1A (p21WAF1/CIP1) degradation."
PLoS Genet. 10:E1004721-E1004721(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation."
Science 326:1707-1711(2009) [PubMed] [Europe PMC] [Abstract]

"Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity."
Am. J. Hum. Genet. 63:1641-1650(1998) [PubMed] [Europe PMC] [Abstract]

"Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors."
Cancer Res. 58:2087-2090(1998) [PubMed] [Europe PMC] [Abstract]

"Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer."
Cancer Res. 58:3787-3790(1998) [PubMed] [Europe PMC] [Abstract]

"STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer."
Cancer Res. 58:4799-4801(1998) [PubMed] [Europe PMC] [Abstract]

"Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome."
Hum. Genet. 103:168-172(1998) [PubMed] [Europe PMC] [Abstract]

"Mutations of the STK11 gene in sporadic gastric carcinoma."
Int. J. Oncol. 13:601-604(1998) [PubMed] [Europe PMC] [Abstract]

"A serine/threonine kinase gene defective in Peutz-Jeghers syndrome."
Nature 391:184-187(1998) [PubMed] [Europe PMC] [Abstract]

"LKB1 somatic mutations in sporadic cancers."
Am. J. Pathol. 154:677-681(1999) [PubMed] [Europe PMC] [Abstract]

"Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families."
Hum. Mutat. 13:476-481(1999) [PubMed] [Europe PMC] [Abstract]

"Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer."
Hum. Mol. Genet. 8:45-51(1999) [PubMed] [Europe PMC] [Abstract]

"Mutational analysis of STK11 gene in ovarian carcinomas."
Jpn. J. Cancer Res. 90:629-632(1999) [PubMed] [Europe PMC] [Abstract]

"Somatic mutations in the Peutz-Jeghers (LKB1/STKII) gene in sporadic malignant melanomas."
J. Invest. Dermatol. 112:509-511(1999) [PubMed] [Europe PMC] [Abstract]

"Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma."
Oncogene 18:1777-1780(1999) [PubMed] [Europe PMC] [Abstract]

"Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients."
Clin. Genet. 62:282-287(2002) [PubMed] [Europe PMC] [Abstract]

"Mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix."
Lab. Invest. 83:35-45(2003) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]

"A novel de novo mutation in LKB1 gene in a Chinese Peutz Jeghers syndrome patient significantly diminished p53 activity."
Clin. Res. Hepatol. Gastroenterol. 35:221-226(2011) [PubMed] [Europe PMC] [Abstract]