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Title

LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes

Authors
Mehenni, Hamid
Lin-Marq, Nathalie
Buchet-Poyau, Karine
Published in Human Molecular Genetics. 2005, vol. 14, no. 15, p. 2209-19
Abstract Germline mutations of the LKB1 (STK11) tumor suppressor gene lead to Peutz-Jeghers syndrome (PJS) and predisposition to cancer. LKB1 encodes a serine/threonine kinase generally inactivated in PJS patients. We identified the dual phosphatase and tumor suppressor protein PTEN as an LKB1-interacting protein. Several LKB1 point mutations associated with PJS disrupt the interaction with PTEN suggesting that the loss of this interaction might contribute to PJS. Although PTEN and LKB1 are predominantly cytoplasmic and nuclear, respectively, their interaction leads to a cytoplasmic relocalization of LKB1. In addition, we show that PTEN is a substrate of the kinase LKB1 in vitro. As PTEN is a dual phosphatase mutated in autosomal inherited disorders with phenotypes similar to those of PJS (Bannayan-Riley-Ruvalcaba syndrome and Cowden disease), our study suggests a functional link between the proteins involved in different hamartomatous polyposis syndromes and emphasizes the central role played by LKB1 as a tumor suppressor in the small intestine.
Keywords Amino Acid SequenceCell Nucleus/enzymologyCells, CulturedCytoplasm/enzymologyGenes, Tumor SuppressorGenetic Predisposition to DiseaseGerm-Line MutationHumansMolecular Sequence DataMutation, MissensePeutz-Jeghers Syndrome/genetics/metabolismPhosphorylationProtein-Serine-Threonine Kinases/genetics/metabolismTwo-Hybrid System Techniques
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PMID: 15987703
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MEHENNI, Hamid et al. LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. In: Human Molecular Genetics, 2005, vol. 14, n° 15, p. 2209-19. https://archive-ouverte.unige.ch/unige:4582

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Deposited on : 2009-12-03

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