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Gene Review

Stk11  -  serine/threonine kinase 11

Mus musculus

Synonyms: AA408040, LKB1, Liver kinase B1 homolog, Lkb1, Par-4, ...
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Disease relevance of Stk11

  • METHODS: Genetic interactions between Cox-2 and Lkb1 in polyp formation were analyzed in mice with combined deficiencies in these genes [1].
  • Here, we demonstrate stromal expression of both COX-2 and microsomal prostaglandin E(2) synthase (mPGES)-1 in gastrointestinal hamartomas developed in Lkb1(+/-), Smad4(+/-) and Cdx2(+/-)mice [2].
  • Here we show that Lkb1(+/-) mice develop intestinal polyps identical to those seen in individuals affected with PJS [3].
  • Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation [3].
  • Here we show that mice with a targeted disruption of Lkb1 die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities [4].

High impact information on Stk11

  • Consistent with this in vivo tumour suppressor function, Lkb1 deficiency prevents culture-induced senescence without loss of Ink4a/Arf or p53 [3].
  • This phenotype is in agreement with the paucity of mutations in Ras seen in PJS polyps and suggests that loss of Lkb1 function as an early neoplastic event renders cells resistant to subsequent oncogene-induced transformation [3].
  • Despite compromised mortality, Lkb1(-/-) mouse embryonic fibroblasts show resistance to transformation by activated Ha-Ras either alone or with immortalizing oncogenes [3].
  • In addition, the Lkb1 transcriptome shows modulation of factors linked to angiogenesis, extracellular matrix remodelling, cell adhesion and inhibition of Ras transformation [3].
  • Pharmacologic inhibition of COX-2 was achieved by supplementing the diet of Lkb1(+/-) mice with 1500 ppm celecoxib between 3.5-10 and 6.5-10 months [1].

Biological context of Stk11

  • Our results indicate that functional Lkb1 is required for normal embryogenesis and that it is related to tumor development [5].
  • Using transfection of Lkb1 cDNAs we have shown that Lkb1 is most likely a nuclear protein and have defined a nuclear localization signal within the protein sequence [6].
  • Although additional genetic events may be critical in hamartoma and adenocarcinoma development, these data strongly suggest that the initiation of polyposis is not the result of loss of heterozygosity in Lkb1 [7].
  • Similar to the Lkb1(+/-) mice, gastrointestinal hamartomas have also been detected in the mice with these two genotypes [8].
  • In Lkb1 (+/-) mice >50 weeks of age, >70% of the male mice developed HCCs, whereas only 20% of the females had HCCs, showing a sex difference in the susceptibility [9].

Anatomical context of Stk11


Other interactions of Stk11

  • The 3" end of Lkb1 in the mouse is in very close proximity to the 3" end of an apparently unrelated gene R29144/1 and it seems probable that overlapping transcripts of the two genes are produced [6].

Analytical, diagnostic and therapeutic context of Stk11


  1. Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2. Udd, L., Katajisto, P., Rossi, D.J., Lepistö, A., Lahesmaa, A.M., Ylikorkala, A., Järvinen, H.J., Ristimäki, A.P., Mäkelä, T.P. Gastroenterology (2004) [Pubmed]
  2. Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomas. Takeda, H., Miyoshi, H., Tamai, Y., Oshima, M., Taketo, M.M. Br. J. Cancer (2004) [Pubmed]
  3. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Bardeesy, N., Sinha, M., Hezel, A.F., Signoretti, S., Hathaway, N.A., Sharpless, N.E., Loda, M., Carrasco, D.R., DePinho, R.A. Nature (2002) [Pubmed]
  4. Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Ylikorkala, A., Rossi, D.J., Korsisaari, N., Luukko, K., Alitalo, K., Henkemeyer, M., Mäkelä, T.P. Science (2001) [Pubmed]
  5. Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in embryogenesis and polyposis. Jishage, K., Nezu, J., Kawase, Y., Iwata, T., Watanabe, M., Miyoshi, A., Ose, A., Habu, K., Kake, T., Kamada, N., Ueda, O., Kinoshita, M., Jenne, D.E., Shimane, M., Suzuki, H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase. Smith, D.P., Spicer, J., Smith, A., Swift, S., Ashworth, A. Hum. Mol. Genet. (1999) [Pubmed]
  7. Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Miyoshi, H., Nakau, M., Ishikawa, T.O., Seldin, M.F., Oshima, M., Taketo, M.M. Cancer Res. (2002) [Pubmed]
  8. Mutation of Lkb1 and p53 genes exert a cooperative effect on tumorigenesis. Wei, C., Amos, C.I., Stephens, L.C., Campos, I., Deng, J.M., Behringer, R.R., Rashid, A., Frazier, M.L. Cancer Res. (2005) [Pubmed]
  9. Hepatocellular carcinoma caused by loss of heterozygosity in Lkb1 gene knockout mice. Nakau, M., Miyoshi, H., Seldin, M.F., Imamura, M., Oshima, M., Taketo, M.M. Cancer Res. (2002) [Pubmed]
  10. Accelerated onsets of gastric hamartomas and hepatic adenomas/carcinomas in Lkb1+/-p53-/- compound mutant mice. Takeda, H., Miyoshi, H., Kojima, Y., Oshima, M., Taketo, M.M. Oncogene (2006) [Pubmed]
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