QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 18 January 2005
doi: 10.1242/jcs.01643

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.01643v1 118/3/601    most recent Alert me when this article is cited Alert me if a correction is posted 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 Tvorogov, D. Articles by Carpenter, G. Search for Related Content PubMed PubMed Citation Articles by Tvorogov, D. Articles by Carpenter, G. Social Bookmarking                         What's this?

Integrin-dependent PLC-1 phosphorylation mediates fibronectin-dependent adhesion

Denis Tvorogov^1,*,, Xue-Jie Wang^1,*,, Roy Zent^2,3 and Graham Carpenter^1,¶

¹ Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
² Departments of Medicine and Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
³ Veterans Affairs Hospital, Nashville, TN 37232, USA

^¶ Author for correspondence (e-mail: graham.carpenter{at}vanderbilt.edu)

Accepted 11 November 2004

Although integrin engagement initiates signaling events such as focal-adhesion kinase (FAK) and Src kinase activation, the role of phosphoinositide turnover in cell adhesion is less clear. To assess PLC-1 function in this process, Plcg1^-/- fibroblasts (Null) were compared with the same fibroblasts in which PLC-1 was re-expressed (Null+). Following plating on fibronectin, Null cells displayed a significantly impaired rate of adhesion compared with Null+ cells. This defect was detected at low concentrations of fibronectin; at high fibronectin concentrations, the Null and Null+ cells displayed equivalent adhesion characteristics. The differences were not due to PLC-1-dependent changes in integrin subunit expression, nor was integrin receptor clustering impaired with the absence of PLC-1. Experiments with site-specific antibodies and PLC-1 mutants showed that fibronectin selectively increased phosphorylation of Tyr783 and that mutagenesis of this residue, but not Tyr771 or Tyr1253, abrogated fibronectin-dependent adhesion. The SH2 domains of PLC-1 were also required for maximal adhesion on fibronectin. Adhesion to fibronectin induced PLC-1 tyrosine phosphorylation that was inhibited by a Src-kinase inhibitor, but not an epidermal-growth-factor-receptor kinase inhibitor. Moreover, in cells null for Src family members, but not in cells null for FAK family members, integrin-dependent PLC-1 tyrosine phosphorylation was greatly reduced. Finally, the data demonstrated that PLC-1 co-immunoprecipitated with Src following fibronectin-induced integrin activation, and this association did not depend on FAK expression.

Key words: PLC-1, Fibronectin, Adhesion, Migration

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

This article has been cited by other articles:

				L. Cao, K. Yu, C. Banh, V. Nguyen, A. Ritz, B. J. Raphael, Y. Kawakami, T. Kawakami, and A. R. Salomon Quantitative Time-Resolved Phosphoproteomic Analysis of Mast Cell Signaling J. Immunol., November 1, 2007; 179(9): 5864 - 5876. [Abstract] [Full Text] [PDF]

				N. P. Jones and M. Katan Role of Phospholipase C{gamma}1 in Cell Spreading Requires Association with a {beta}-Pix/GIT1-Containing Complex, Leading to Activation of Cdc42 and Rac1 Mol. Cell. Biol., August 15, 2007; 27(16): 5790 - 5805. [Abstract] [Full Text] [PDF]

				Y. Wang, A. Tomar, S. P. George, and S. Khurana Obligatory role for phospholipase C-{gamma}1 in villin-induced epithelial cell migration Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1775 - C1786. [Abstract] [Full Text] [PDF]