Activation of protein kinase C via the T-cell receptor complex potentiates cyclic AMP responses in T-cells.
We have recently shown that activation of protein kinase C by tumour promoting phorbolesters, such as 4 beta-phorbol-12,13-dibutyrate, stimulates adenosine-induced accumulation of cAMP in Jurkat cells, a human T-leukaemia line. Activating the CD3 complex associated with the T-cell receptor by means of the monoclonal antibody OKT3 caused a concentration-dependent accumulation of inositol phosphates and an increase in the phosphorylation of an endogenous protein kinase C substrate. OKT3 also mimicked the previously reported effects of protein kinase C since it potentiated the cAMP stimulation by either an adenosine analogue, NECA, or cholera toxin. Thus, our results indicate that stimulation of a receptor activating phospholipase C and protein kinase C can secondarily enhance the action of agonists that act on adenylate cyclase-coupled receptors.
Kvanta
A
A
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nordstedt
C
C
Jondal
M
M
Fredholm
B B
BB
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D015240:Phorbol 12,13-Dibutyrate; D007294:Inositol; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000241:Adenosine