Polymyxin B causes coordinate inhibition of phorbol ester-induced C-kinase activity and proliferation of B lymphocytes.
Lymphocytes were found to be rich in phospholipid/Ca2+-dependent (C-kinase) activity. Addition of polymyxin B (PMB) to in vitro assays of endogenous and exogenous phosphorylation resulted in profound inhibition of C-kinase activity. The phorbol ester 12-o-tetradecanoyl phorbol-13-acetate (TPA) directly activated C-kinase, leading to increased phosphorylation of the same substrates. TPA also stimulated proliferation of B cells as assessed by 3H-thymidine uptake, and PMB strongly inhibited this effect. This coordinate inhibition of TPA-induced phosphorylation and mitogenesis indicates that PMB is a potentially useful inhibitor of C-kinase activity, and that this enzyme may play an important role in mediating B cell responses.
Nel
A E
AE
Wooten
M W
MW
Goldschmidt-Clermont
P J
PJ
Miller
P J
PJ
Stevenson
H C
HC
Galbraith
R M
RM
D001402:B-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D010704:Phorbols / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D010718:Phosphatidylserines; D011113:Polymyxins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D011493:Protein Kinase C; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium