The Gi-protein as a Target for Receptor-Receptor Interactions
The hormone-sensitive adenylate cyclase system, which serves as a transmembrane signal transduction system for a wide variety of hormones and neurotransmitters, is a dually regulated signalling system. On the one hand, many hormonal agents, after interaction with their specific receptors, cause an increase in cyclic AMP formation by the adenylate cyclase. This action is mediated by the stimulatory guanine nucleotide-binding regulatory component Gs, which transfers the information from the hormone-activated receptor to the adenylate cyclase. On the other hand, a similarly large number of hormonal agents, after interaction with their specific receptors, induce inhibition of cyclic AMP formation by the adenylate cyclase. This action involves the coupling function of the inhibitory guanine nucleotide-binding regulatory component Gi. Thus, the hormone-sensitive adenylate cyclase by itself is a system exhibiting receptor-receptor interaction, at least at the level of the adenylate cyclase, in that the action of one receptor (stimulatory or inhibitory to the adenylate cyclase) on cyclic AMP formation can be modulated by activation of another set of receptors (inhibitory or stimulatory to the adenylate cyclase).
KeywordsLymphoma Polypeptide Prostaglandin Epinephrine Sine
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- Aktories, K. and Jakobs, K.H. (1985). Regulation of platelet cyclic AMP formation. In The Platelets: Physiology and Pharmacology. (ed. G.L. Longenecker). Academic Press, Orlando.Google Scholar
- Birnbaumer, L., Codina, J., Mattera, R., Cerione, R.A., Hildebrandt, J.D., Sunyer, T., Rojas, F.J., Caron, M.G., Lefkowitz, R.J. and Iyengar, R. (1985). Regulation of hormone receptors and adenylyl cyclases by guanine nucleotide binding N proteins. Rec. Progr. Hormone Res., 41, 41–94.Google Scholar
- Jakobs, K.H., Aktories, K. and Schultz, G. (1984). Mechanisms and components involved in adenylate cyclase inhibition by hormones. Adv. Cyclic Nucleotide Protein Phosphoryl. Res., 17, 135–143.Google Scholar
- Jakobs, K.H., Aktories, K., Minuth, M. and Schultz, G. (1985). Inhibition of adenylate cyclase. Adv. Cyclic Nucleotide Protein Phosphoryl. Res., 19,137–150.Google Scholar
- Jakobs, K.H., Bauer, S. and Watanabe, Y. (1985a). Modulation of adenylate cyclase of human platelets by phorbol ester. Impairment of the hormone-sensitive inhibitory pathway. Eur. J. Biochem., 151,425–430.Google Scholar
- Katada, T., Gilman, A.G., Watanabe, Y., Bauer, S. and Jakobs, K.H. (1985). Protein kinase C phosphorylates the inhibitory gua-nine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur. J. Biochem., 151, 431–437.PubMedCrossRefGoogle Scholar
- Takai, Y., Kikkawa, U., Kaibuchi, K. and Nishizuka, Y. (1984).Google Scholar
- Membrane phospholipid metabolism and signal transduction for protein phosphorylation. Adv. Cyclic Nucleotide Protein Phosphoryl. Res., 18, 119–158.Google Scholar
- Ui, M., Katada, T., Murayama, T., Kurose, H., Yajima, M., Tamura, M., Nakamura, T. and Nogimori, K. (1984). Islet-activating protein, pertussis toxin: A specific uncoupler of receptor-mediated inhibition of adenylate cyclase. Adv. Cyclic Nuc-leotide Protein Phosphoryl. Res., 17,145–151.Google Scholar
- Watanabe, Y., Horn, F., Bauer, S. and Jakobs, K.H. (1985). Protein kinase C interferes with Ni-mediated inhibition of human platelet adenylate cyclase. FEBS Lett., 192,23–27.Google Scholar