DIFFERENTIAL-EFFECTS OF THE TYROSINE KINASE INHIBITORS ON COLLAGEN TYPE 1-INDUCED PLATELET-AGGREGATION AND ADHESION TO THIS PROTEIN

Herbimycin A, lavendustin A, and methyl 2,5-dihydroxycinnamate were us ed to study the role of protein tyrosine kinases in collagen-platelet interaction. All three compounds produced a concentration dependent in hibition of platelet aggregation induced by collagen type I, character ized by values of IC50 equaled to 0.9, 10.0, and 5.0 mu M, respectivel y. This effect was accompanied by strong inhibition of phosphorylation of p125(FAK), p90, p72(syk), p60(c-src), and p56(lyn). In the absence of the inhibitors, phosphorylation of these proteins is evoked by agg regation of platelets. In addition to the antiaggregatory effect, the tyrosine kinase inhibitors reduced adhesion of platelets to collagen a lthough to much lower extent than aggregation. Platelets which adhered to collagen showed also the presence of phosphorylated p125(FAK), p90 , p72(syk), p60(c-src), and p56(lyn). Of these proteins, the extent of phosphorylation of p90 was particularly high. Adhesion of platelets w as associated with inhibition of phosphorylation of p125(FAK), p60(c-s rc), and p56(lyn) only when high concentration of lavendustin A and me thyl 2,5-dihydroxycinnamate were used. Herbimycin A did not affect adh esion-evoked protein tyrosine phosphorylation. Phosphorylation of p90 and p72(syk) was not affected by inhibitors. This study indicates that collagen type I can induce different transmembrane signalling depende nt upon whether platelet aggregates formation or adhesion of platelets to this protein occurs. (C) 1997 Elsevier Science Ltd.