Activation of human platelet MAP kinase by genistein

Stimulation of mitogen-activated protein kinase (MAPK), implicated in cell growth and proliferation, was studied in human platelets, non-proliferating cells. Protein kinase C (PKC)-dependent activation of MAPK was studied using PMA, which increased the MAPK activity in a dose- and time-dependent manner. Surprisingly, tyrosine kinase inhibitors (genistein, tyrphostin, and methyl 2,5-dihydroxycinnamate) also stimulated the MAPK activity. The activation of MAPK by genistein was investigated in detail. The activation of MAPK by genistein seems to be restricted to platelets since in other cell types tested (i.e., HEL, BNLCL2 and U937) genistein failed to activate MAPK. Furthermore, it was demonstrated that intact platelets are required. The activation of platelet MAPK by genistein was apparently independent of cAMP- or PKC-mediated signal transduction pathways. Based on a number of pharmacological evidence presented in this thesis, it is proposed that genistein inhibited pp60...