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.
Koike
T
T
Department of Biochemistry, Gifu University School of Medicine, Japan.
Mizutani
T
T
Hirai
K
K
Morita
Y
Y
Nozawa
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D019833:Genistein; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000378:metabolism*; D019089:Stem Cell Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D004075:Diglycerides; D016298:Hematopoietic Cell Growth Factors; D007529:Isoflavones; D009227:Myristic Acids; D010713:Phosphatidylcholines; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019814:Myristic Acid; D016718:Arachidonic Acid; D014638:Vanadates; D011433:Propranolol; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate