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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-05-1703.
Submitted May 28, 2003
Accepted July 14, 2003
Calcium- and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen
Meghna U Naik and Ulhas P Naik*
Department of Biological Sciences, University of Delaware, Newark, DE, USA
* Corresponding author; email: unaik{at}udel.edu.
Platelet spreading on the subendothelium in response to vascular injury is fundamental to the regulation of physiological hemostasis. Previously we have shown that, when bound to GPIIb, calcium- and integrin-binding (CIB) protein regulates platelet spreading on immobilized fibrinogen (Fg). In this study, we investigated the signaling events that occur downstream of CIB in the absence of signaling that occurs as a result of granular secretion. Using CHO cells as a model, we demonstrate that CIB induces cell migration. Immunofluorescence analysis of CIB localization indicates that endogenous CIB accumulates in areas of focal adhesions, and its overexpression upregulates the formation of focal adhesion complexes compared to control cells. Immunoprecipitation analysis indicates that CIB associates with focal adhesion kinase (FAK), a key regulator in focal complex formation, and upregulates its activity. Overexpression of dominant-negative FAK, FRNK, along with CIB in CHO cells completely inhibits CIB-induced cell migration. Further, confirmation of these data in the platelet system indicates that CIB and FAK associate throughout all stages of platelet spreading, but only upon Fg binding to GPIIb/IIIa. Taken together, our results suggest that CIB regulates platelet spreading through the regulation of FAK activation.
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