SCF/C-KIT RECEPTOR-MEDIATED ARACHIDONIC-ACID LIBERATION IN RAT MAST-CELLS - INVOLVEMENT OF PLD ACTIVATION-ASSOCIATED TYROSINE PHOSPHORYLATION

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. © 1993 Academic Press, Inc.