STK11 (serine/threonine kinase 11)

2007-01-01   Bharati Bapat , Sheron Perera 

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Department of Lab Medicine, Pathobiology, University of Toronto, Canada





10 Exons spanning 23 kb, the 10th exon occurs within the 3 untranslated region of the gene. The gene is transcribed in telomere to centromere direction.


The length of this transcript has not been reconciled. The curated human Vega transcript is the longest transcript reported to date (3,627 bp, Vega external transcript). The GeneBank sequence is the same but is shorter (3,286 bp) at the 3 end (NM_000455.4). The exon/intron structures in GeneBank are given for 2 alternative assemblies (aligned with NT_011255.14 and NW_927173.1), of which the NT_0112255.14 is consistent with the Vega annotation. Alternative transcripts although shown to occur, have not be been well characterized.


Atlas Image
Diagram of STK11 protein (not drawn to scale). The kinase domain is depicted by the green box. The second box outlined by the dashed lines illustrates the location of the nuclear localization signal (NLS) and the purple box indicates the prenylation motif. This protein is believed to contain a putative cytoplasmic retention signal (not shown).


433 amino acids, 48.6 kDa; N-term with a nuclear localization domain and a putative cytoplasmic retention signal, a kinase domain, and a C-terminal CAAX box prenylation motif.


Ubiquitous, especially high expression in the testis and fetal liver.


Found in both the nucleus and the cytoplasm. Localization is thought to be dependent on interaction with proteins such as BRG1, LIP1, STRAD, MO25.


A serine/threonine protein kinase, recently classified as a part of the Ca2+/ calmodulin kinase group of kinases. STK11 was shown to associate and activate the pseudokinase, STRAD, resulting in the reorganization of non-polarized cells so they form asymmetrical apical and basal structures. Another mechanism by which this may occur is by the interaction of STK11 with the PAR1 family of serine/threonine kinases. AMPK is a protein kinase cascade that plays an important role in regulating energy homeostasis. The first report of an upstream regulator came when it was discovered that STK11, in complex with STRAD and the scaffolding protein MO25, can phosphorylate and activate AMPK. Subsequently, it was demonstrated that STK11 can phosphorylate the T-loop of 12 other AMPK related human kinases. In addition it has been implicated in a range of processes including, chromatin remodeling, cell cycle arrest, ras-induced cell transformation, p53-mediated apoptosis and Wnt signaling.


Orthologs found in several species and include:
Xenopus laevis egg and embryonic kinase 1(XEEK1),
Caenorhabditis elegans partitioning defective gene 4 (PAR4),
mouse LKB1
and drosophila LKB1.



Most mutations identified to date are in the catalytic domain of STK11, indicating that kinase activity is likely essential for its function as a tumor suppressor. Several types of mutations including insertions, deletions, nonsense, missense and splice site alterations have been identified to date. One family has been identified with complete germline deletion of this gene.


Many of the polyps that develop in Peutz-Jeghers syndrome (see below) show loss of heterozygosity and sometimes somatic mutations. Somatic mutations rarely occur in sporadic tumours, with the exception of adenocarcinoma of the lung. The inactivation of the LKB1 can also occur through promoter hypermethylation.

Implicated in

Entity name
Peutz-Jeghers syndrome (PJS)
Autosomal dominant syndrome associated with mucocutaneous hyperpigmentation and benign intestinal polyps known as hamartomas. The relative incidence is estimated to vary from 1/29 000 to 1/120 000 births. Patients are at an increased risk of developing malignancies in epithelial tissues, for example it has been estimated that there is a about 84, about 213 and about 520 fold increased risk of developing colon, gastric and small intestinal cancers respectively. PJS patients are also at an increased risk of developing cancers in the breast, lung, ovaries, uterus, cervix and testes.
Hybrid gene
A majority (60-70%) of Peutz-Jeghers patients show germline mutations in STK11. Genetic locus heterogeneity may exist for this disease. A small percentage of families with no mutations in STK11/LKB1 have been identified, however no other candidate genes that predispose to Peutz-Jeghers syndrome have been identified to date.
Patients inherit mutations in one allele, and the remaining allele is later inactivated generally by LOH or sometimes somatic mutation. This biallelic inactivation of STK11 leads to a loss of tumour suppressor activity, thereby promoting tumourigenesis.
Entity name
Lung adenocarcinoma
Adenocarcinoma is the most common non-small-cell lung cancer accounting for about 30-40% of all cases diagnosed to date. These tumors are thought to derive from epithelial cells that line the peripheral small airways and the heterogeneity of lung tumours is well documented. The outcome of non-small cell lung cancer is more difficult to predict, and about 50% of patients die from metastatic disease even after surgery of the primary tumour.
Hybrid gene
As many as 33% of sporadic lesions analyzed display somatic mutations in STK11.
Loss of protein function is seen in sporadic lung adenocarcinoma tumours.


Pubmed IDLast YearTitleAuthors
151217682004Genotype-phenotype correlations in Peutz-Jeghers syndrome.Amos CI et al
128052202003Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD.Baas AF et al
150163792004Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD.Baas AF et al
122266642002Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation.Bardeesy N et al
106449932000Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome.Esteller M et al
94287651998A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.Hemminki A et al
94258971998Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.Jenne DE et al
114308322001The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death.Karuman P et al
149765522004LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.Lizcano JM et al
156234752005LKB1, the multitasking tumour suppressor kinase.Marignani PA et al
112975202001Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth.Sapkota GP et al
165806342006The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA-6, and Ldb1.Setogawa T et al
117418302001LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1.Smith DP et al
151867632004LKB1 kinase: master and commander of metabolism and polarity.Spicer J et al
128790202003Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1.Spicer J et al
104309281999Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest.Tiainen M et al
115097332001Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice.Ylikorkala A et al

Other Information

Locus ID:

NCBI: 6794
MIM: 602216
HGNC: 11389
Ensembl: ENSG00000118046


dbSNP: 6794
ClinVar: 6794
TCGA: ENSG00000118046


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
Tight junctionKEGGko04530
Adipocytokine signaling pathwayKEGGko04920
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
Tight junctionKEGGhsa04530
Adipocytokine signaling pathwayKEGGhsa04920
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
FoxO signaling pathwayKEGGhsa04068
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
Signal TransductionREACTOMER-HSA-162582
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
PKB-mediated eventsREACTOMER-HSA-109703
mTOR signallingREACTOMER-HSA-165159
Energy dependent regulation of mTOR by LKB1-AMPKREACTOMER-HSA-380972
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Integration of energy metabolismREACTOMER-HSA-163685
AMPK inhibits chREBP transcriptional activation activityREACTOMER-HSA-163680
Longevity regulating pathwayKEGGhsa04211
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through PhosphorylationREACTOMER-HSA-6804756

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA445307Peutz-Jeghers SyndromeDiseaseLiterature, MultilinkAnnotationassociated23788249


Pubmed IDYearTitleCitations
149855052004The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress.634
149765522004LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.481
176760352007LKB1 modulates lung cancer differentiation and metastasis.405
186876772008SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation.247
120972712002Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.209
120972712002Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.209
128472912003Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases.199
152317352004Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome.170
202273672010MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells.165
128052202003Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD.130


Bharati Bapat ; Sheron Perera

STK11 (serine/threonine kinase 11)

Atlas Genet Cytogenet Oncol Haematol. 2007-01-01

Online version:

Historical Card

2002-02-01 STK11 (serine/threonine kinase 11) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France