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-γ1 function in this process, Plcg1-/- fibroblasts (Null) were compared with the same fibroblasts in which PLC-γ1 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-γ1-dependent changes in integrin subunit expression, nor was integrin receptor clustering impaired with the absence of PLC-γ1. Experiments with site-specific antibodies and PLC-γ1 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-γ1 were also required for maximal adhesion on fibronectin. Adhesion to fibronectin induced PLC-γ1 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-γ1 tyrosine phosphorylation was greatly reduced. Finally, the data demonstrated that PLC-γ1 co-immunoprecipitated with Src following fibronectin-induced integrin activation, and this association did not depend on FAK expression.
Integrin-dependent PLC-γ1 phosphorylation mediates fibronectin-dependent adhesion
These authors contributed equally to this work
Present address: MediCity Research Laboratory Tykistokatu 6A, Turku, Finland
Present address: Department of Technology Development, Biology, Discover Research, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA
Denis Tvorogov, Xue-Jie Wang, Roy Zent, Graham Carpenter; Integrin-dependent PLC-γ1 phosphorylation mediates fibronectin-dependent adhesion. J Cell Sci 1 February 2005; 118 (3): 601–610. doi: https://doi.org/10.1242/jcs.01643
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