On the tyrosine kinase mechanism of the novel effect of insulin and insulinlike growth factor I. Stimulation of the adenylyl cyclase system in muscle tissues.
For the first time, insulinlike growth factor I (IGF-I), like insulin (Pertseva et al., Comp Biochem Physiol 112: 689-695, 1995), was shown to exercise a GTP-dependent stimulating action on adenylyl cyclase (AC; EC 4.6.1.1.) activity in the muscle tissues (membrane fraction) of mammal (rat) and mollusc (Anodonta cygnea). By studying the mechanism of the effect of peptides with selective inhibitors of tyrosine kinase activity, tyrphostin 47 (RG50864, 3,4-dihydroxy-alpha-cyanothiocinnamamide) and genistein (4,5,7-trihydroxyisoflavone), it was found that receptor tyrosine kinase is involved in this action. The data obtained suggest that the stimulating effect of insulin and IGF-1 is produced via the following signalling system: receptor tyrosine kinase --> stimulatory G-protein --> AC. Thus, the existence of a novel signalling pathway of transduction of signals generated by insulin and related peptides was hypothesised.
Pertseva
M N
MN
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Plesneva
S A
SA
Kuznetsova
L A
LA
Shpakov
A O
AO
Derkach
K V
KV
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D049872:Bivalvia; D000242:Cyclic AMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D019833:Genistein; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009132:Muscles / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D020032:Tyrphostins
D004791:Enzyme Inhibitors; D007328:Insulin; D007529:Isoflavones; D009570:Nitriles; D010636:Phenols; D020032:Tyrphostins; C060152:tyrphostin 47; D006165:Guanylyl Imidodiphosphate; D007334:Insulin-Like Growth Factor I; D019833:Genistein; D000242:Cyclic AMP; D020794:Receptor Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases