ACTIVATION OF PROTEIN-TYROSINE KINASE SYK IN HUMAN PLATELETS STIMULATED WITH LYSOPHOSPHATIDIC ACID OR SPHINGOSINE 1-PHOSPHATE

It has been reported that not only lysophosphatidic acid (LPA) but als o its sphingolipid counterpart, sphingosine 1-phosphate (Sph-1-P), ind uce platelet functional responses. We report here Syk activation in hu man platelets stimulated with these lysophospholipids. LPA rapidly ind uced platelet protein-tyrosine phosphorylation, including that of Syk, and Syk activation, assessed by immunoprecipitation kinase assay. Sph -1-P, although rather weaker, mimicked LPA in inducing these tyrosine kinase-related events. Pretreatment of platelets with staurosporine, a potent protein kinase inhibitor, diminished LPA-induced Syk phosphory lation and activation, but not intracellular Ca2+ mobilization. These results demonstrate that, in platelets, the bioactive lysophospholipid s induce Syk activation, which, however, may not be related to Ca(2+)m obilization. (C) 1996 Academic Press, Inc.