Protein kinase C activation blocks anti-IgM-mediated signaling BAL17 B lymphoma cells.
Short term pretreatment of the B lymphoma, BAL17, with phorbol 12-myristate, 13-acetate (PMA) blocks elevation in inositol trisphosphate (InsP3) and increases in intracellular free calcium concentration ([Ca2+]i) in response to anti-IgM. The inhibition of enhanced InsP3 level is detected at 30 sec after the addition of anti-IgM, the earliest point measured, and is reversed by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, an inhibitor of protein kinase C (PKC). The blockade of increased [Ca2+]i by PMA is also observed at the earliest time examined (15 sec), is reversed by 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride, and is mimicked by dioctanoylglycerol, a physiologic activator of PKC. The enhanced production of inositol phosphates in response to NaF is also blocked in BAL17 cells pretreated with PMA. Extended treatment of BAL17 cells with PMA depletes cellular PKC. Such pretreatment with PMA enhances rather than inhibits increased InsP3 levels in response to anti-IgM and leads to more sustained elevations in [Ca2+]i than in normal BAL17 cells. These results lead us to conclude that PMA-blockade of the response of B cells to anti-IgM represents a disruption of the transmembrane signaling process (desensitization of the signaling pathway) as a result of a PKC-mediated phosphorylation event.
D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D007075:Immunoglobulin M / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008223:Lymphoma; D010716:Phosphatidylinositols / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D004075:Diglycerides; D007075:Immunoglobulin M; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium