A dual role of protein kinase C in insulin signal transduction via adenylyl cyclase signaling system in muscle tissues of vertebrates and invertebrates

Further decoding of a novel adenylyl cyclase signaling mechanism (ACSM) of the action of insulin and related peptides detected earlier (Pertseva er al . Comp Biochem Physiol B Biochem Mol Biol 1995;112:689-95 and Pertseva et a l. Biochem Pharmacol 1996;52: 1867-74) was carried out with special attenti on given to the role of protein kinase C (PKC) in the ACSM. It was shown fo r the first time that transduction of the insulin signal via the ACSM follo wed by adenylyl cyclase (AC, EC 4.6.1.1) activation was blocked in the musc le tissues of rat and mollusc Anodonta cygnea in the presence of pertussis toxin, inducing the impairment of G(i)-protein function, wortmannin, an inh ibitor of phosphatidylinositol 3-kinase (PI3-K), and calphostin C, a blocke r of PKC. The cholera toxin treatment of muscle membranes led to an increas e in basal AC activity and a decrease in enzyme insulin reactivity. Phorbol eater and diacylglycerol activation of PKC (acute treatment) induced the i nhibition of the insulin AC activating effect. This negative influence was also observed in the case of the AC system activated by biogenic amines. It was first concluded that the ACSM of insulin action involves the following signaling chain: receptor tyrosine kinase double right arrow G(i) (beta ga mma) double right arrow PI3-K double right arrow PKC zeta (?) double right arrow G(s) double right arrow AC double right arrow adenosine 3',5'-cyclic monophosphate. It was also concluded that the PKC system has a dual role in the ACSM: (l)a regulatory role (PKC sensitive to phorbol esters) that is m anifested as a negative feedback modulation of insulin signal transduction via the ACSM; (2) a transductory role, which consists in direct participati on of atypical PKC (PKC zeta) in the process of insulin signal transduction via the ACSM. (C) 2001 Elsevier Science Inc. All rights reserved.