A dual role of protein kinase C in insulin signal transduction via adenylyl cyclase signaling system in muscle tissues of vertebrates and invertebrates11Abbreviations: PKC, protein kinase C (α, λ, ε, ϕ, ζ, its isoforms); AC, adenylyl cyclase (EC 4.6.1.1); AC I, II, etc. (isoforms of AC); ACSM, adenylyl cyclase signaling mechanism; DAG, diacylglycerol; PE, phorbol esters; PMA, phorbol 12-myristate 13-acetate; PI3-K, phosphatidylinositol 3-kinase; Gs-protein, stimulatory GTP-binding protein; Gi-protein, inhibitory GTP-binding protein; α, β, γ, the subunits of G-proteins; IGF-I, insulin-like growth factor-I; PT, pertussis toxin; ChT, cholera toxin; Gpp[NH]p, 5′-guanylylimidodiphosphate; DTT, dithiothreitol; and cAMP, adenosine 3′,5′-cyclic monophosphate

Further decoding of a novel adenylyl cyclase signaling mechanism (ACSM) of the action of insulin and related peptides detected earlier (Pertseva et al . Comp Biochem Physiol B Biochem Mol Biol 1995;112:689–95 and Pertseva et al . Biochem Pharmacol 1996;52:1867–74) was carried out with special attention given to the role of protein kinase C (PKC) in the ACSM. It was shown for the first time that transduction of the insulin signal via the ACSM followed by adenylyl cyclase (AC, EC 4.6.1.1) activation was blocked in the muscle tissues of rat and mollusc Anodonta cygnea in the presence of pertussis toxin, inducing the impairment of G i -protein function, wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), and calphostin C, a blocker of PKC. The cholera toxin treatment of muscle membranes led to an increase in basal AC activity and a decrease in enzyme insulin reactivity. Phorbol ester and diacylglycerol activation of PKC (acute treatment) induced the inhibition 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 ⇒ G i (βγ) ⇒ PI3-K ⇒ PKCζ (?) ⇒ G s ⇒ AC ⇒ adenosine 3′,5′-cyclic monophosphate. It was also concluded that the PKC system has a dual role in the ACSM: (1) a regulatory role (PKC sensitive to phorbol esters) that is manifested as a negative feedback modulation of insulin signal transduction via the ACSM; (2) a transductory role, which consists in direct participation of atypical PKC (PKCζ) in the process of insulin signal transduction via the ACSM.