HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 32, 28936-28943, August 12, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/32/28936    most recent M504761200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Valiente, M. Articles by Pulido, R. Search for Related Content PubMed PubMed Citation Articles by Valiente, M. Articles by Pulido, R. Social Bookmarking                      What's this?

Binding of PTEN to Specific PDZ Domains Contributes to PTEN Protein Stability and Phosphorylation by Microtubule-associated Serine/Threonine Kinases^*

Miguel Valiente, Amparo Andrés-Pons, Beatriz Gomar¶, Josema Torres¶||, Anabel Gil, Caroline Tapparel**, Stylianos E. Antonarakis**, and Rafael Pulido

From the Centro de Investigación Príncipe Felipe, Valencia 46013, Spain and ^**Division of Medical Genetics, Centre Medical Universitaire, University of Geneva Medical School, 1 Rue Michel Servet, Geneva CH-1211, Switzerland

The tumor suppressor phosphatase PTEN is a key regulator of cell growth and apoptosis that interacts with PDZ domains from regulatory proteins, including MAGI-1/2/3, hDlg, and MAST205. Here we identified novel PTEN-binding PDZ domains within the MAST205-related proteins, syntrophin-associated serine/threonine kinase and MAST3, characterized the regions of PTEN involved in its interaction with distinctive PDZ domains, and analyzed the functional consequences on PTEN of PDZ domain binding. Using a panel of PTEN mutations, as well as PTEN chimeras containing distinct domains of the related protein TPTE, we found that the PTP and C2 domains of PTEN do not affect PDZ domain binding and that the C-terminal tail of PTEN (residues 350–403) provides selectivity to recognize specific PDZ domains from MAGI-2, hDlg, and MAST205. Binding of PTEN to the PDZ-2 domain from MAGI-2 increased PTEN protein stability. Furthermore, binding of PTEN to the PDZ domains from microtubule-associated serine/threonine kinases facilitated PTEN phosphorylation at its C terminus by these kinases. Our results suggest an important role for the C-terminal region of PTEN in the selective association with scaffolding and/or regulatory molecules and provide evidence that PDZ domain binding stabilizes PTEN and targets this tumor suppressor for phosphorylation by microtubule-associated serine/threonine kinases.

Received for publication, April 29, 2005 , and in revised form, June 7, 2005.

^* This work was supported in part by Grant SAF2002-00085 from Ministerio de Ciencia y Tecnología and Fondo Europeo de Desarrollo Regional and by a grant from Fundación Mutua Madrileña Automovilista (Spain). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a fellowship from Ministerio de Educación y Ciencia (Spain).

^¶ Recipient of a fellowship from Generalitat Valenciana (Spain).

^|| Present address: Keratinocyte Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WCA 3PX, UK.

To whom correspondence should be addressed: Centro de Investigación Príncipe Felipe, Avda. Autopista del Saler, 16-3, 46013 Valencia, Spain. Tel.: 34-96-3289680; Fax: 34-96-3289701; E-mail: rpulido{at}ochoa.fib.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Ikenoue, K. Inoki, B. Zhao, and K.-L. Guan PTEN Acetylation Modulates Its Interaction with PDZ Domain Cancer Res., September 1, 2008; 68(17): 6908 - 6912. [Abstract] [Full Text] [PDF]

				T. Tamguney and D. Stokoe New insights into PTEN J. Cell Sci., December 1, 2007; 120(23): 4071 - 4079. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				S. Balasubramanian, S. R. Fam, and R. A. Hall GABAB Receptor Association with the PDZ Scaffold Mupp1 Alters Receptor Stability and Function J. Biol. Chem., February 9, 2007; 282(6): 4162 - 4171. [Abstract] [Full Text] [PDF]

				R. S. Nho, H. Xia, D. Diebold, J. Kahm, J. Kleidon, E. White, and C. A. Henke PTEN Regulates Fibroblast Elimination during Collagen Matrix Contraction J. Biol. Chem., November 3, 2006; 281(44): 33291 - 33301. [Abstract] [Full Text] [PDF]

				F. Okahara, K. Itoh, A. Nakagawara, M. Murakami, Y. Kanaho, and T. Maehama Critical Role of PICT-1, a Tumor Suppressor Candidate, in Phosphatidylinositol 3,4,5-Trisphosphate Signals and Tumorigenic Transformation Mol. Biol. Cell, November 1, 2006; 17(11): 4888 - 4895. [Abstract] [Full Text] [PDF]

				A. Gil, A. Andres-Pons, E. Fernandez, M. Valiente, J. Torres, J. Cervera, and R. Pulido Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs Mol. Biol. Cell, September 1, 2006; 17(9): 4002 - 4013. [Abstract] [Full Text] [PDF]

				M.-A. Arevalo and A. Rodriguez-Tebar Activation of Casein Kinase II and Inhibition of Phosphatase and Tensin Homologue Deleted on Chromosome 10 Phosphatase by Nerve Growth Factor/p75NTR Inhibit Glycogen Synthase Kinase-3beta and Stimulate Axonal Growth Mol. Biol. Cell, August 1, 2006; 17(8): 3369 - 3377. [Abstract] [Full Text] [PDF]

				F. Edwin, R. Singh, R. Endersby, S. J. Baker, and T. B. Patel The Tumor Suppressor PTEN Is Necessary for Human Sprouty 2-mediated Inhibition of Cell Proliferation J. Biol. Chem., February 24, 2006; 281(8): 4816 - 4822. [Abstract] [Full Text] [PDF]

				A. M. Al-Khouri, Y. Ma, S. H. Togo, S. Williams, and T. Mustelin Cooperative Phosphorylation of the Tumor Suppressor Phosphatase and Tensin Homologue (PTEN) by Casein Kinases and Glycogen Synthase Kinase 3{beta} J. Biol. Chem., October 21, 2005; 280(42): 35195 - 35202. [Abstract] [Full Text] [PDF]