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 hormone containing the sequence H2N-Leu-Ser-Arg-Leu-Phe-Asu11-Asn-Ala-COOH (Asu11-hGH 6-13) on tyrosine kinase of rat hepatic insulin receptors was examined. Insulin receptor kinase activity was evaluated using the synthetic polypeptide poly(Glu-Tyr)(4:1) as substrate. The hypoglycaemic Asu11-hGH 6-13 appeared to enhance the phosphorylation of the exogenous substrate by the stimulation of insulin receptor kinase activity. The levels of poly(Glu-Tyr)(4:1) phosphorylation were significantly higher in the insulin receptor preparations incubated in the presence of the Asu11-hGH 6-13 peptide. A dose dependent stimulation of receptor kinase activity was observed and this stimulatory effect was found to be further enhanced by the addition of increasing concentrations of insulin. In hepatic extracts depleted of insulin receptor, no stimulation of kinase activity by the Asu11-hGH 6-13 was observed. From these data, it is concluded that the increase of poly (Glu-Tyr) (4:1) phosphorylation is the result of the interaction between the Asu11-hGH 6-13 and the hepatic insulin receptor.
Lim
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N
Department of Biochemistry, Monash University, Clayton, Victoria, Australia.
Wijaya
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E
Ng
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D011972:Receptor, Insulin / Q000378:metabolism*; D013379:Substrate Specificity
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D013006:Growth Hormone; D011972:Receptor, Insulin