Stem cell factor-induced signal transduction in rat mast cells. Activation of phospholipase D but not phosphoinositide-specific phospholipase C in c-kit receptor stimulation.
Stem cell factor (SCF), a hematopoietic growth factor for primitive hematopoietic stem cells, is also known as mast cell growth factor. SCF induced serotonin release from rat peritoneal mast cells, connective tissue-type mast cells. The treatment of rat peritoneal mast cells with SCF failed to produce inositol 1,4,5-trisphosphate, indicating the absence of involvement of phosphoinositide-specific phospholipase C pathway. 1,2-Diacylglycerol (1,2-DG) and phosphatidic acid, however, were increased after stimulation by SCF. Phosphatidylethanol formation catalyzed by phospholipase D (PLD) was observed, together with the release of choline but not phosphocholine. Propranolol, an inhibitor of phosphatidate phosphohydrolase, blocked the production of 1,2-DG. These results indicate that the phosphatidylcholine-specific PLD pathway is the main pathway for the production of 1,2-DG in SCF-stimulated rat peritoneal mast cells. Furthermore, treatment of cells with protein tyrosine kinase inhibitor, genistein, inhibited 1,2-DG formation and serotonin release dose-dependently. Taken together, SCF induces the activation of PLD through the protein tyrosine kinase pathway without activation of phosphoinositide-specific phospholipase C.
Koike
T
T
Department of Biochemistry, Gifu University School of Medicine, Japan.
Hirai
K
K
Morita
Y
Y
Nozawa
Y
Y
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D004075:Diglycerides / Q000378:metabolism; D019833:Genistein; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D019000:Phosphotyrosine; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D019089:Stem Cell Factor; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000941:Antigens; D004075:Diglycerides; D016298:Hematopoietic Cell Growth Factors; D007529:Isoflavones; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; D019000:Phosphotyrosine; D012701:Serotonin; D014443:Tyrosine; D019833:Genistein; D019009:Proto-Oncogene Proteins c-kit; D010738:Type C Phospholipases; D010739:Phospholipase D