SYNTHESIS OF PHOSPHATIDYLINOSITOL 3,4-BISPHOSPHATE BUT NOT PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IS CLOSELY CORRELATED WITH PROTEIN-TYROSINE PHOSPHORYLATION IN THROMBIN-ACTIVATED HUMAN PLATELETS

Synthesis of D-3-phosphorylated phosphoinositides and its correlation with protein-tyrosine phosphorylation were examined using human platelets. Thrombin stimulation of platelets resulted in time- and dose-dependent production of phosphatidylinositol 3,4-bisphosphate (Ptdlns(3,4)P2), which is absent from resting platelets. In contrast, phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P3) was detected in resting platelets, but remained unaffected by thrombin treatment. The production of Ptdlns(3,4)P2 but not Ptdlns(3,4,5)P3 was inhibited by pretreatment with staurosporine or dibutyryl cyclic adenosine monophosphate (dbcAMP). Protein-tyrosine phosphorylation, which is reportedly involved in generation of 3-phosphorylated phosphoinositides, was elicited in thrombin-activated platelets. The tyrosine phosphorylation was suppressed by pretreatment with staurosporine or dbcAMP. These observations suggest that synthesis of Ptdlns(3,4)P2 but not Ptdlns(3,4,5)P3 is closely correlated with protein-tyrosine phosphorylation in human platelets. © 1992 Academic Press, Inc.