STIMULATION OF INSULIN-RECEPTOR TYROSINE KINASE-ACTIVITY BY AN AMINO-TERMINAL SEQUENCE OF HUMAN GROWTH-HORMONE

The in vitro effect of a hypoglycaemic fragment of human growth hormon e containing the sequence H2N-Leu-Ser-Arg-Leu-Phe-Asu(11)-Asn-Ala-COOH (Asu(11)-hGH 6-13) on tyrosine kinase of rat hepatic insulin receptor s was examined. Insulin receptor kinase activity was evaluated using t he synthetic polypeptide poly(Glu-Tyr)(4:1) as substrate. The hypoglyc aemic Asu(11)-hGH 6-13 appeared to enhance the phosphorylation of the exogenous substrate by the stimulation of insulin receptor kinase acti vity. The levels of poly(Glu-Tyr)(4:1) phosphorylation were significan tly higher in the insulin receptor preparations incubated in the prese nce of the Asu(11)-hGH 6-13 peptide. A dose dependent stimulation of r eceptor kinase activity was observed and this stimulatory effect was f ound to be further enhanced by the addition of increasing concentratio ns of insulin. In hepatic extracts depleted of insulin receptor, no st imulation of kinase activity by the Asu(11)-hGH 6-13 was observed. Fro m these data, it is concluded that the increase of poly (Glu-Tyr)(4:1) phosphorylation is the result of the interaction between the Asu(11)- hGH 6-13 and the hepatic insulin receptor.