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STK11

GeneName

STK11

Summary

STK11, also known as LKB1 or liver kinase B1, is a serine/threonine protein kinase that plays a vital role in various cellular processes. It is expressed in multiple tissues and localised in the cytoplasm, nucleus, mitochondria, and membrane. STK11 is involved in the regulation of metabolic pathways, cell growth, and polarity, and has been implicated in the DNA damage response and autophagy. It is known to activate protein kinase activity and is associated with the regulation of the Wnt signalling pathway and the intrinsic apoptotic signalling pathway mediated by p53. The protein interacts with several cellular components, including centrosomes and cilia, and is essential for maintaining glucose homeostasis and tissue homeostasis.

Importance

STK11 is relevant to: - Cancer research, particularly in lung cancer and Peutz-Jeghers syndrome, due to its role as a tumour suppressor and regulator of cell proliferation - Metabolic disorders, as it influences glucose homeostasis and energy metabolism - Neurodegenerative diseases through its involvement in autophagy and neuronal development - Developmental biology, given its role in cell polarity and differentiation during tissue development

Top Products

For researchers investigating STK11, we recommend two excellent primary antibodies that cater to various experimental needs. The first is the well-cited Anti-LKB1 antibody [Ley 37D/G6] (ab15095), a monoclonal antibody that has garnered 41 citations, highlighting its reliability in Western blotting (WB). This antibody has also been validated in knockout models, ensuring its effectiveness in specific applications. In addition, we offer the recombinant antibody, Anti-LKB1 antibody [EPR19379] (ab199970), which is suitable for both WB and immunoprecipitation (IP). With 13 citations, this product is also validated in knockout models, making it a robust choice for researchers seeking the consistency and performance that recombinant antibodies provide. Together, these antibodies represent a strong toolkit for studying STK11. The Anti-LKB1 antibody ELISA Kit (ab199970), supported by 13 citations, is an excellent option for researchers looking to accurately measure STK11 levels in their samples.

Abcam Product Citation Summary

The data indicates that the STK11 target is primarily studied in human contexts, particularly in relation to cancer, such as cervical and lung cancer. The antibody ab15095 has been used extensively in Western Blotting and Immunohistochemistry applications, highlighting its relevance in cancer research and cellular studies.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab15095
Mouse
IHC
Uterus
24086281
ab15095
Human
IHC
Cervical cancer cell lines
24086281
ab15095
Human
WB
Lung cancer cell lines
27266881
ab15095
Human
WB
LKB1 gene expression
22412893
ab15095
Human
WB
Cell lines
22412893
ab15095
Human
WB
HEK293 cell lysates
28636940

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 (PubMed:25329316).

Isoform 2

Has a role in spermiogenesis.

Involvement in disease

Peutz-Jeghers syndrome

PJS

An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer.

None

The disease is caused by variants affecting the gene represented in this entry.

Testicular germ cell tumor

TGCT

A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.

None

The gene represented in this entry may be involved in disease pathogenesis.

Defects in STK11 are associated with some sporadic cancers, especially lung cancers. Frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis process, especially lung cancer progression and metastasis. Confers lung adenocarcinoma the ability to trans-differentiate into squamous cell carcinoma. Also able to promote lung cancer metastasis, via both cancer-cell autonomous and non-cancer-cell autonomous mechanisms.

Post-translational modifications

Phosphorylated by ATM at Thr-363 following ionizing radiation (IR). Phosphorylation at Ser-428 by RPS6KA1 and/or some PKA is required to inhibit cell growth. Phosphorylation at Ser-428 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2 (By similarity). Phosphorylation by PKC/PRKCZ at Ser-399 in isoform 2 promotes metformin (or peroxynitrite)-induced nuclear export of STK11 and activation of AMPK. UV radiation-induced phosphorylation at Thr-363 mediates CDKN1A degradation (By similarity).

Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.

Sequence Similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.

Tissue Specificity

Ubiquitously expressed. Strongest expression in testis and fetal liver.

Cellular localization

Alternative names

LKB1, PJS, STK11, Serine/threonine-protein kinase STK11, Liver kinase B1, Renal carcinoma antigen NY-REN-19, hLKB1

swissprot:Q15831 entrezGene:6794 omim:602216

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