SCF/c-kit receptor-mediated arachidonic acid liberation in rat mast cells. Involvement of PLD activation associated tyrosine phosphorylation.

Abstract We have previously demonstrated PLD activation via c- kit receptor activation in rat peritoneal mast cells (Koike et al. 1993, J. Immunol. 151, 359-366). In this study, the mechanism of arachidonic acid (AA) release in stem cell factor (SCF) stimulation was investigated. Genistein, a protein tyrosine kinase inhibitor, was found to inhibit the AA release in SCF-stimulated cells, whereas pretreatment with vanadate, a protein tyrosine phosphatase inhibitor, enhanced the AA release. Propranolol. an inhibitor of phosphatidate (PA) phosphohydrolase. repressed both AA liberation and 1,2-diacylglycerol (1,2-DG) formation. Short pretreatment with phorbol myristate acetate blunted the SCF-induced AA liberation. These results indicate that 1,2-DG generated via the phospholipase D pathway activated by tyrosine phosphorylation is a principle source for AA released in response to SCF in mast cells.