Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion.

Tvorogov D, Wang XJ, Zent R, Carpenter G
J Cell Sci. 2005 118 (Pt 3): 601-10

PMID: 15657076 · DOI:10.1242/jcs.01643

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-gamma1 function in this process, Plcg1(-/-) fibroblasts (Null) were compared with the same fibroblasts in which PLC-gamma1 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-gamma1-dependent changes in integrin subunit expression, nor was integrin receptor clustering impaired with the absence of PLC-gamma1. Experiments with site-specific antibodies and PLC-gamma1 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-gamma1 were also required for maximal adhesion on fibronectin. Adhesion to fibronectin induced PLC-gamma1 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-gamma1 tyrosine phosphorylation was greatly reduced. Finally, the data demonstrated that PLC-gamma1 co-immunoprecipitated with Src following fibronectin-induced integrin activation, and this association did not depend on FAK expression.

MeSH Terms (19)

Animals Cell Adhesion Cell Line Cell Movement Fibroblasts Fibronectins Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Integrin beta1 Integrins Mice Mice, Knockout Phospholipase C gamma Phosphorylation Protein-Tyrosine Kinases Protein Binding src-Family Kinases Type C Phospholipases Tyrosine

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