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Human Molecular Genetics Advance Access originally published online on June 29, 2005
Human Molecular Genetics 2005 14(15):2209-2219; doi:10.1093/hmg/ddi225
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

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

Hamid Mehenni1,2,*, Nathalie Lin-Marq2, Karine Buchet-Poyau2,{dagger}, Alexandre Reymond2,{ddagger}, Martine A. Collart3, Didier Picard1,¶ and Stylianos E. Antonarakis2,¶

1Département de Biologie Cellulaire, Université de Genève, 1211 Genève 4, Switzerland, 2Département de Médecine Génétique et Développement and 3Département de Microbiologie et Médecine Moléculaire, Université de Genève, Centre Médical Universitaire, 1211 Genève 4, Switzerland

* To whom correspondence should be addressed at: Département de Biologie Cellulaire, Université de Genève, Sciences 3, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland. Tel: +41 223796811; Fax: +41 223281157; Email: mehenni{at}cellbio.unige.ch

Received June 8, 2005; Accepted June 17, 2005

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.

{dagger} Present address. Laboratoire Génétique Moléculaire, Signalisation et Cancer, CNRS UMR 5201, Domaine Rockefeller-Université Lyon 1, 8 Avenue Rockefeller, 69008 Lyon, France.

{ddagger} Present address. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.

These authors contributed equally to this work.


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