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

J. Biol. Chem., Vol. 283, Issue 7, 4344-4351, February 15, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/7/4344    most recent M706550200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gomes, D. A. Articles by Nathanson, M. H. Search for Related Content PubMed PubMed Citation Articles by Gomes, D. A. Articles by Nathanson, M. H. Related Collections Papers Of The Week Social Bookmarking                      What's this?

c-Met Must Translocate to the Nucleus to Initiate Calcium Signals^*

Dawidson A. Gomes, Michele A. Rodrigues, M. Fatima Leite, Marcus V. Gomez^¶, Peter Varnai^||, Tamas Balla^||, Anton M. Bennett^**, and Michael H. Nathanson¹

From the Department of Internal Medicine and ^**Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8019, the Department of Physiology and Biophysics and ^¶Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, MG, CEP 31270-901 Brazil, and the ^||Section on Molecular Signal Transduction, NICHD/National Institutes of Health, Bethesda, Maryland 20892

Hepatocyte growth factor (HGF) is important for cell proliferation, differentiation, and related activities. HGF acts through its receptor c-Met, which activates downstream signaling pathways. HGF binds to c-Met at the plasma membrane, where it is generally believed that c-Met signaling is initiated. Here we report that c-Met rapidly translocates to the nucleus upon stimulation with HGF. Ca²⁺ signals that are induced by HGF result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus depends upon the adaptor protein Gab1 and importin β1, and formation of Ca²⁺ signals in turn depends upon this translocation. HGF may exert its particular effects on cells because it bypasses signaling pathways in the cytoplasm to directly activate signaling pathways in the nucleus.

Received for publication, August 7, 2007 , and in revised form, October 15, 2007.

^* This work was supported by National Institutes of Health Grants DK57751, DK34989, and DK45710, and by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico. Fundaçao de Amparo à Pesquisa do Estado de Minas Gerais, and Howard Hughes Medical Institute. 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.

This article was selected as a Paper of the Week.

¹ To whom correspondence should be addressed: Digestive Diseases, Rm. TAC S241D, Yale University School of Medicine, New Haven, CT 06520-8019. Tel.: 203-785-7312; Fax: 203-785-4306; E-mail: michael.nathanson{at}yale.edu.

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

This article has been cited by other articles:

				F. Ginty, S. Adak, A. Can, M. Gerdes, M. Larsen, H. Cline, R. Filkins, Z. Pang, Q. Li, and M. C. Montalto The Relative Distribution of Membranous and Cytoplasmic Met Is a Prognostic Indicator in Stage I and II Colon Cancer Clin. Cancer Res., June 15, 2008; 14(12): 3814 - 3822. [Abstract] [Full Text] [PDF]