Tyrosine kinase-dependent phosphatidylinostiol turnover and functional responses in the Fc epsilon R1 signalling pathway.
In RBL-2H3 rat basophilic leukemia cells, Fc epsilon R1 crosslinking by multivalent antigen stimulates phosphatidylinositol (PI) turnover and Ca2+ influx and causes functional responses that include secretion, membrane ruffling and actin polymerization. Here, we show that the tyrosine kinase inhibitor, genistein, inhibits antigen-induced PI turnover, determined from assays of 1,4,5-inositol trisphosphate production, and impairs receptor-mediated secretion, ruffling and actin polymerization. Genistein has little effect on several functional responses to stimuli that bypass PI hydrolysis (ionomycin-induced secretion, phorbol ester-induced ruffling) but it inhibits phorbol ester-induced actin polymerization. These data implicate a common tyrosine kinase-dependent event, most likely the activation of phospholipase C gamma, in the Fc epsilon R1-mediated stimulation of PI turnover, secretion and ruffling. There may be additional tyrosine kinase-mediated events in the actin assembly pathway.
Deanin
G G
GG
Department of Pathology, University of New Mexico, Albuquerque 87131.
Martinez
A M
AM
Pfeiffer
J R
JR
Gardner
M E
ME
Oliver
J M
JM
D000199:Actins / Q000378:metabolism; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D002460:Cell Line; D019833:Genistein; D007073:Immunoglobulin E / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D010716:Phosphatidylinositols / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction
D000199:Actins; D000944:Antigens, Differentiation, B-Lymphocyte; D007529:Isoflavones; D010716:Phosphatidylinositols; D011961:Receptors, Fc; D017455:Receptors, IgE; D012701:Serotonin; D007073:Immunoglobulin E; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D019833:Genistein; D011505:Protein-Tyrosine Kinases