A novel fetal insulin-like growth factor (IGF) I receptor. Mechanism for increased IGF I- and insulin-stimulated tyrosine kinase activity in fetal muscle.
Insulin and insulin-like growth factor (IGF) I receptors from fetal and adult rat skeletal muscle were compared in order to gain insight into the evolving functions of the hormones during development. Basal, insulin-stimulated, and IGF I-stimulated receptor phosphorylation and tyrosine kinase activity are severalfold higher in partially purified receptor preparations from fetal muscle in comparison with equal numbers of receptors from adult muscle. There are distinct insulin and IGF I receptors with Mr 95,000 beta subunits in adult muscle, as evidenced by hormone dose-response curves, immunoprecipitation with specific antibodies, binding to insulin and IGF I affinity columns, and analysis of tryptic phosphopeptides. In addition to these two receptor species, fetal muscle contains a receptor with a Mr 105,000 beta subunit. The fetal receptor is structurally more closely related to the IGF-I receptor than the insulin receptor on the basis of its precipitation with specific antibodies, binding to an IGF I affinity column, and tryptic phosphopeptide map. The fetal receptor does not appear to bind insulin but, unlike the IGF-I receptor, its phosphorylation is stimulated by low physiological concentrations of both insulin and IGF I. This could be explained by the cross-phosphorylation of fetal receptors by activated insulin receptors. Expression of the fetal receptor is highest in the fetus and decreases markedly during the first 2 weeks of postnatal life. The fetal receptor appears to account for the high tyrosine kinase activity of fetal muscle and may be an important mediator of responses to both insulin and IGF I early in development.
Alexandrides
T K
TK
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215.
Smith
R J
RJ
D000327:Adsorption; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002847:Chromatography, Agarose; D005314:Embryonic and Fetal Development; D005260:Female; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009132:Muscles / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D014357:Trypsin
D007328:Insulin; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D014357:Trypsin