title: Characterization of insulin-like growth factor I-stimulated tyrosine kinase activity associated with the beta-subunit of type I insulin-like growth factor receptors of rat liver cells.
abstract: We previously reported that insulin-like growth factor I (IGF-I) stimulates the phosphorylation of a Mr 98,000 protein thought to be the beta-subunit of the type I IGF receptor of BRL-3A2 rat liver cells, as well as phosphorylation of the exogenous tyrosine-containing substrate poly(Glu,Tyr), 4:1. The present study provides additional evidence that the type I IGF receptor possesses intrinsic tyrosine kinase activity and characterizes the properties of this receptor kinase. IGF-I stimulates receptor phosphorylation and phosphorylation of poly(Glu,Tyr), 4:1, by lectin-purified receptor preparations with the same concentration dependence; half-maximal stimulation was observed with approximately 3 nM IGF-I and approximately 3-fold higher concentrations of insulin. Although IGF-I-dependent receptor phosphorylation was observed within 2 min and was maximal after 10 min, phosphorylation of exogenous substrate did not begin to increase until 8 min after addition of [gamma-32P] ATP and poly(Glu,Tyr), 4:1. When IGF-I-receptor complexes were preincubated with unlabeled ATP for 10 min before addition of substrate, however, IGF-I-dependent 32P incorporation was observed within 2 min after addition of poly(Glu,Tyr), 4:1, and increased linearly for 20 min. We propose that this activation of type I IGF receptor tyrosine kinase activity results from autophosphorylation of the receptor kinase. Kinase activation is an intramolecular reaction, is specific for ATP, occurs within 3 min after addition of unlabeled ATP, and requires the presence of IGF-I before or concomitant with activation by ATP. IGF-I acts rapidly, stimulating substrate phosphorylation within 3 min. The properties of the type I-IGF receptor kinase closely resemble those of the insulin receptor kinase, suggesting that the homologies between the two receptors extend to their kinase domains.
authors.forename: N
authors.initials: N
authors.lastname: Sasaki
authors.forename: R W
authors.initials: RW
authors.lastname: Rees-Jones
authors.forename: Y
authors.initials: Y
authors.lastname: Zick
authors.forename: S P
authors.initials: SP
authors.lastname: Nissley
authors.forename: M M
authors.initials: MM
authors.lastname: Rechler
mesh_terms: D000818:Animals; D007328:Insulin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000032:analysis*; D046911:Macromolecular Substances; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009711:Nucleotides / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D013379:Substrate Specificity; D013997:Time Factors
chemical_list: D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D009711:Nucleotides; D010455:Peptides; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; C027606:L-glutamic acid-L-tyrosine copolymer; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D008274:Magnesium