Platelet adhesion and signaling induced by the octapeptide primary binding sequence (KOGEOGPK) from type III collagen.

Platelet adhesion to vascular collagens is an essential step in the initiation of hemostasis and thrombosis. Several platelet receptors interact with type I and type III collagens, including GP Ia/IIa and GP VI. We recently described a new platelet receptor (TIIICBP) specific for a type III collagen-related primary binding sequence, the KOGEOGPK octapeptide. Here, we characterize platelet adhesion to the immobilized octapeptide and demonstrate that this adhesion 1) is Ca2+ and Mg2+ independent, suggesting a noninvolvement of GP Ia/IIa; 2) is not inhibited by an antibody against GP VI; and 3) triggers platelet protein tyrosine phosphorylation. Whereas TXA2 has minimal effects, released ADP via only P2Y12 potentiates platelet adhesion to the octapeptide. Octapeptide-induced platelet adhesion triggers platelet signaling through tyrosine phosphorylation of the 68 kDa subunit of TIIICBP, Syk, PLCgamma2, and FAK. Tyrosine phosphorylation of the FcR gamma-chain and LAT is also observed but to a lesser extent than with type III collagen, suggesting the requirement of GP VI for full tyrosine phosphorylation of FcR gamma-chain and LAT. The present study provides evidence for a critical role for the type III collagen-related KOGEOGPK octapeptide in mediating platelet adhesion and signaling, and consequently in platelet-collagen interactions.-