ECHISTATIN INHIBITS PP72(SYK) AND PP125(FAK) PHOSPHORYLATION IN FIBRINOGEN-ADHERENT PLATELETS

The adhesion of ADP-stimulated platelets to immobilized fibrinogen ind uces the tyrosine phosphorylation of multiple proteins which include p p7(syk) and pp125(FAK). Th, phosphorylation of these two proteins incr eases as function of time of platelet adhesion to fibrinogen; however, pp72(syk) results strongly phosphorylated already after 15 min, where as pp125(FAK) reaches high levels of phosphorylation after 1 h of plat elet adhesion. Phosphorylation of both proteins is only slightly detec table when platelets are held in suspension or when platelets are allo wed to adhere to bovine serum albumin, a non-specific substrate. Echis tatin, an Arg-Gly-Asp (RGD)-containing snake-venom protein, affects pr otein tyrosine phosphorylation promoted by platelet adhesion to fibrin ogen, by causing an approximately 44% and 39% decrease of pp72(syk) an d pp125(FAK) phosphorylation, respectively. The interaction of echista tin with fibrinogen receptor glycoprotein IIb-IIIa on platelet surface might be responsible for the block of integrin-mediated signaling cas cade, including pp72(syk) and pp125(FAK) inactivation.