Dual effects of protein kinase-C on receptor-stimulated cAMP accumulation in a human T-cell leukemia line.
In the human T-cell leukemia line Jurkat, cAMP accumulation stimulated by the adenosine receptor agonist 5'-N-ethylcarboxamido adenosine (NECA) was enhanced by tumour-promoting phorbol esters whereas the prostaglandin receptor-stimulated accumulation of cAMP was antagonized. Phorbol esters did not alter the adenosine or prostaglandin receptor-stimulated accumulation of cAMP in cells in which the phospholipid/Ca2+-dependent protein kinase (protein kinase-C) was down-regulated. cAMP stimulation induced by cholera toxin (CT) was enhanced by phorbol esters by 100-300%. The cAMP production induced by forskolin was never enhanced by more than 50% by 4 beta-phorbol-12,13-dibutyrate (PDBu) and there was no stimulation at all after down-regulation of the adenosine receptor by treatment with NECA. Phorbol ester enhanced the NECA-stimulated accumulation of cAMP, even in the presence of concentrations of forskolin that increased the cAMP accumulation several-fold. From these data we conclude that protein kinase-C can interact with receptors coupled to adenylate cyclase in a stimulatory as well as an inhibitory manner. Moreover, protein kinase-C appears to interact with signal transduction at two levels, one highly receptor-specific and one distal to the receptor.
Nordstedt
C
C
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Kvanta
A
A
Van der Ploeg
I
I
Fredholm
B B
BB
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*
D010703:Phorbol Esters; D011982:Receptors, Prostaglandin; D011983:Receptors, Purinergic; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000241:Adenosine; D015232:Dinoprostone