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

Détails

ID Serval
serval:BIB_23DD6AA4A6BF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes.
Périodique
Human Molecular Genetics
Auteur(s)
Mehenni H., Lin-Marq N., Buchet-Poyau K., Reymond A., Collart M.A., Picard D., Antonarakis S.E.
ISSN
0964-6906[print], 0964-6906[linking]
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
14
Numéro
15
Pages
2209-2219
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Amino Acid Sequence, Cell Nucleus/enzymology, Cells, Cultured, Cytoplasm/enzymology, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Molecular Sequence Data, Mutation, Missense, Peutz-Jeghers Syndrome/genetics, Peutz-Jeghers Syndrome/metabolism, Phosphorylation, Protein-Serine-Threonine Kinases/genetics, Protein-Serine-Threonine Kinases/metabolism, Two-Hybrid System Techniques
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:52
Dernière modification de la notice
20/08/2019 14:01
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