The role of tyrosine phosphorylation in signal transduction through surface Ig in human B cells. Inhibition of tyrosine phosphorylation prevents intracellular calcium release.
Cross-linking surface Ig on human B cells, or the TCR complex on T cells leads to the rapid appearance of newly tyrosine phosphorylated proteins. This is associated with inositol phospholipid turnover and a rise in intracellular calcium. Incubation of human B or T lymphocytes with the tyrosine kinase inhibitors, herbimycin and genistein, inhibits new tyrosine phosphorylation after receptor-linked activation. This is associated with complete abrogation of the increase in intracellular calcium in these lymphocytes and inhibition of inositol phospholipid turnover. Herbimycin- and genistein-treated lymphocytes are nevertheless still capable of responding to aluminum fluoride with a rise in intracellular calcium. These data support the contention that a B cell-associated protein tyrosine kinase regulates signal transduction via phospholipase C. CD45, the membrane associated protein tyrosine phosphatase, and PMA that activates protein kinase C, both inhibit the calcium response in B lymphocytes induced by receptor cross-linking. PMA and cross-linking CD45 both induced the appearance of tyrosine phosphorylated proteins in human B cells, although the pattern is quite distinct from that seen when surface lg is cross-linked. However, the induction of new tyrosine phosphorylation by anti-mu does not appear to be affected by these reagents. Although this may reflect an insensitivity of the tyrosine phosphorylation assay, it could indicate that regulation of the calcium response and regulation of the tyrosine kinase can be independent processes.
Regional Primate Research Center, University of Washington, Seattle 98195.
P J
PJ
Lane
J A
JA
Ledbetter
F M
FM
McConnell
K
K
Draves
J
J
Deans
G L
GL
Schieven
E A
EA
Clark
D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016227:Benzoquinones; D019013:CD40 Antigens; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003432:Cross-Linking Reagents; D005459:Fluorides / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008954:Models, Biological; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017607:Aluminum Compounds; D000944:Antigens, Differentiation, B-Lymphocyte; D016227:Benzoquinones; D019013:CD40 Antigens; D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D011947:Receptors, Antigen, B-Cell; D017828:Rifabutin; D019000:Phosphotyrosine; D014443:Tyrosine; C020754:herbimycin; D000535:Aluminum; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride