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PubMed · 2165756

Cross-talk between second messengers.

M Bouvier
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Abstract

Cells are under the continuous influence of a variety of simultaneous stimulations. A coherent and organized cellular response therefore presupposes the existence of fine integration mechanisms. Cross-talk between different signaling pathways could contribute to such integration. Receptor-mediated activation of the adenylyl cyclase and phosphatidyl-inositides hydrolysis systems represent two ubiquitous signaling pathways that served as a model to study cross-talk between second messengers. Stimulations of the phosphatidyl-inositides turnover pathway as well as direct activation of protein kinase C by phorbol esters have been reported to modulate the beta-adrenergic-stimulated adenylyl cyclase activity. To study the molecular basis of this regulatory process, several models were used. In avian erythrocytes, phorbol esters treatment induces a desensitization of the beta-adrenergic-stimulated adenylyl cyclase. This desensitization is accompanied by an increased phosphorylation of the beta-adrenergic receptor. Moreover, the purified beta 2-adrenergic receptor is a substrate in vitro for protein kinase C. This suggests that phosphorylation of the beta-adrenergic receptor by protein kinase C could contribute to the desensitization of the beta-adrenergic-stimulated adenylyl cyclase activity mediated by phosphatidyl-inositides turnover coupled receptors. In contrast with what is observed in avian erythrocytes, treatment of frog erythrocytes with phorbol esters leads to an enhancement of the adenylyl cyclase activity stimulated by beta-adrenergic agonists, fluoride or GTP. In these cells, phorbol esters treatment induces a dramatic increase in the level of phosphorylation of the adenylyl cyclase catalytic unit. Moreover purified protein kinase C can directly phosphorylate the catalytic unit of adenylyl cyclase in vitro. Such phosphorylation induces a significant increase of the Gpp(NH)p-stimulated activity of the enzyme. These results provide a plausible explanation for the increased cyclase activity observed in frog erythrocytes following phorbol esters treatment. Therefore, receptor-mediated stimulation of phosphatidyl-inositides turnover appears to modulate the beta-adrenergic-stimulated adenylyl cyclase activity via protein kinase C-mediated phosphorylation of distinct components of the cAMP production system.

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Adenylyl CyclasesAnimalsGTP-Binding ProteinsHumansPhosphorylationReceptors, Cell SurfaceSecond Messenger SystemsJournal ArticleReview

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BibTeXRIS

M Bouvier. 1990. Cross-talk between second messengers.. https://doi.org/10.1111/j.1749-6632.1990.tb40473.x

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