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Dual effects of protein kinase-C on receptor-stimulated cAMP accumulation in a human T-cell leukemia line

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Abstract

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 cellsiin which the phospholipid/Ca2+-dependent protein kinase (protein kinase-C) was down-regulated. cAMP stimulation induced by cholera toxin (CC) was enhanced by phorbol esters by 100–300%. The cAMP production induced by forskolin was never enhanced by more than 50% by 4β-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.

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