STK11
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| Location (UCSC) | Chr 19: 1.18 – 1.23 Mb | Chr 10: 79.95 – 79.97 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.[5]
Expression
However, in ER-positive breast cancer cell line MCF-7, estradiol caused a dose-dependent decrease in LKB1 transcript and protein expression leading to a significant decrease in the phosphorylation of the LKB1 target AMPK.
Function
The STK11/LKB1 gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumour suppressor.
LKB1 is a primary upstream kinase of adenosine 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 ~14 other 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.[8][9] A study in rats showed that LKB1 expression is upregulated in cardiomyocytes after birth and that LKB1 abundance negatively correlates with proliferation of neonatal rat cardiomyocytes.[10]
Loss of LKB1 activity is associated with highly aggressive HER2+ breast cancer.
LKB1 catalytic deficient mutants found in
Clinical significance
At least 51 disease-causing mutations in this gene have been discovered.
LKB1 has been implicated as a potential target for inducing cardiac regeneration after injury as the regenerative potential of cardiomyocytes is limited in adult mammals. Knockdown of Lkb1 in rat cardiomyocytes suppressed phosphorylation of AMPK and activated Yes-associated protein, which subsequently promoted cardiomyocyte proliferation.[21]
Activation
LKB1 is activated
Structure
The crystal structure of the LKB1-STRAD-MO25 complex was elucidated using
Splice variants
Alternate transcriptional
Interactions
STK11 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000118046 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000003068 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 28986057.
- PMID 21876548.
- S2CID 25221068.
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- PMID 24062587.
- S2CID 248465561.
- ^ PMID 23451056.
- PMID 25436981.
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- S2CID 8978401.
- S2CID 4400728.
- PMID 18846624.
- PMID 12097271.
- PMID 17599048.
- ^ "Distribution of somatic mutations in STK11". Catalogue of Somatic Mutations in Cancer. Wellcome Trust Genome Campus, Hinxton, Cambridge. Archived from the original on 2012-04-02. Retrieved 2009-11-11.
- S2CID 248465561.
- PMID 17921699.
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- ^ PMID 12489981.
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Further reading
- Yoo LI, Chung DC, Yuan J (July 2002). "LKB1--a master tumour suppressor of the small intestine and beyond". Nature Reviews. Cancer. 2 (7): 529–35. S2CID 43512220.
- Baas AF, Smit L, Clevers H (June 2004). "LKB1 tumor suppressor protein: PARtaker in cell polarity". Trends in Cell Biology. 14 (6): 312–9. PMID 15183188.
- Katajisto P, Vallenius T, Vaahtomeri K, Ekman N, Udd L, Tiainen M, Mäkelä TP (January 2007). "The LKB1 tumor suppressor kinase in human disease". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1775 (1): 63–75. PMID 17010524.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Bignell GR, Barfoot R, Seal S, Collins N, Warren W, Stratton MR (April 1998). "Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer". Cancer Research. 58 (7): 1384–6. PMID 9537235.
- Nakagawa H, Koyama K, Miyoshi Y, Ando H, Baba S, Watatani M, et al. (August 1998). "Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome". Human Genetics. 103 (2): 168–72. S2CID 23986504.
- Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. (December 1998). "Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity". American Journal of Human Genetics. 63 (6): 1641–50. PMID 9837816.
- Guldberg P, thor Straten P, Ahrenkiel V, Seremet T, Kirkin AF, Zeuthen J (March 1999). "Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma". Oncogene. 18 (9): 1777–80. PMID 10208439.
- Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, et al. (June 1999). "Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers". The American Journal of Pathology. 154 (6): 1835–40. PMID 10362809.
- Westerman AM, Entius MM, Boor PP, Koole R, de Baar E, Offerhaus GJ, et al. (1999). "Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families". Human Mutation. 13 (6): 476–81. S2CID 27714949.
- Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, et al. (November 1999). "Antigens recognized by autologous antibody in patients with renal-cell carcinoma". International Journal of Cancer. 83 (4): 456–64. PMID 10508479.
- Collins SP, Reoma JL, Gamm DM, Uhler MD (February 2000). "LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo". The Biochemical Journal. 345 Pt 3 (3): 673–80. PMID 10642527.
- Sapkota GP, Kieloch A, Lizcano JM, Lain S, Arthur JS, Williams MR, et al. (June 2001). "Phosphorylation 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". The Journal of Biological Chemistry. 276 (22): 19469–82. PMID 11297520.
- Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, et al. (June 2001). "The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death". Molecular Cell. 7 (6): 1307–19. PMID 11430832.
- Carretero J, Medina PP, Pio R, Montuenga LM, Sanchez-Cespedes M (May 2004). "Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene". Oncogene. 23 (22): 4037–40. PMID 15021901.
- Abed AA, Günther K, Kraus C, Hohenberger W, Ballhausen WG (November 2001). "Mutation screening at the RNA level of the STK11/LKB1 gene in Peutz-Jeghers syndrome reveals complex splicing abnormalities and a novel mRNA isoform (STK11 c.597(insertion mark)598insIVS4)". Human Mutation. 18 (5): 397–410. S2CID 39255354.
- Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, et al. (December 2001). "STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas". The American Journal of Pathology. 159 (6): 2017–22. PMID 11733352.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
