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

J. Biol. Chem., Vol. 280, Issue 30, 27631-27637, July 29, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/30/27631    most recent M504189200v1 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 Xu, Z. Articles by Wu, C. Search for Related Content PubMed PubMed Citation Articles by Xu, Z. Articles by Wu, C. Social Bookmarking                      What's this?

Molecular Dissection of PINCH-1 Reveals a Mechanism of Coupling and Uncoupling of Cell Shape Modulation and Survival^*

Zhen Xu, Tomohiko Fukuda, You Li, Xiliang Zha¶, Jun Qin||, and Chuanyue Wu**

From the Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, ^¶Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China, and ^||Structural Biology Program, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195

How cells couple and uncouple regulation of cellular processes such as shape change and survival is an important question in molecular cell biology. PINCH-1, a widely expressed protein consisting of five LIM domains and a C-terminal tail, is an essential focal adhesion protein with multiple functions including regulation of the integrin-linked kinase (ILK) level, cell shape, and survival signaling. We show here that the LIM1-mediated interaction with ILK regulates all these three processes. By contrast, the LIM4-mediated interaction with Nck-2, which regulates cell morphology and migration, is not required for the control of the ILK level and survival. Remarkably, a short 15-residue tail C-terminal to LIM5 is required for both cell shape modulation and survival, albeit it is not required for the control of the ILK level. The C-terminal tail not only regulates PINCH-1 localization to focal adhesions but also functions after it localizes there. These findings suggest that PINCH-1 functions as a molecular platform for coupling and uncoupling diverse cellular processes via overlapping but yet distinct domain interactions.

Received for publication, April 18, 2005 , and in revised form, May 31, 2005.

^* This work was supported by National Institutes of Health Grants GM65188 and DK54639 (to C. W.) and HL58758 (to J. Q.). 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.

Both authors contributed equally to this work.

This paper is in memory of Zhen Xu, who passed away after this work was completed.

^** To whom correspondence should be addressed: 707B Scaife Hall, Dept. of Pathology, University of Pittsburgh, 3550 Terrace St., Pittsburgh, PA 15261. Tel.: 412-648-2350; Fax: 509-561-4062; E-mail: carywu{at}pitt.edu.

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

This article has been cited by other articles:

				S. E. Quaggin and J. A. Kreidberg Development of the renal glomerulus: good neighbors and good fences Development, February 15, 2008; 135(4): 609 - 620. [Abstract] [Full Text] [PDF]

				K. Chen, Y. Tu, Y. Zhang, H. C. Blair, L. Zhang, and C. Wu PINCH-1 Regulates the ERK-Bim Pathway and Contributes to Apoptosis Resistance in Cancer Cells J. Biol. Chem., February 1, 2008; 283(5): 2508 - 2517. [Abstract] [Full Text] [PDF]

				J. Cheng, J. Zhang, A. Merched, L. Zhang, P. Zhang, L. Truong, A. M. Boriek, and J. Du Mechanical Stretch Inhibits Oxidized Low Density Lipoprotein-induced Apoptosis in Vascular Smooth Muscle Cells by Up-regulating Integrin {alpha}Vbeta3 and Stablization of PINCH-1 J. Biol. Chem., November 23, 2007; 282(47): 34268 - 34275. [Abstract] [Full Text] [PDF]

				K. Mori, M. Asakawa, M. Hayashi, M. Imura, T. Ohki, E. Hirao, J.-r. Kim-Kaneyama, K. Nose, and M. Shibanuma Oligomerizing Potential of a Focal Adhesion LIM Protein Hic-5 Organizing a Nuclear-Cytoplasmic Shuttling Complex J. Biol. Chem., August 4, 2006; 281(31): 22048 - 22061. [Abstract] [Full Text] [PDF]

				F. Stanchi, R. Bordoy, O. Kudlacek, A. Braun, A. Pfeifer, M. Moser, and R. Fassler Consequences of loss of PINCH2 expression in mice J. Cell Sci., December 15, 2005; 118(24): 5899 - 5910. [Abstract] [Full Text] [PDF]