Hepatic insulin and EGF receptor phosphorylation and dephosphorylation in fetal rats.
Hepatic insulin receptor and epidermal growth factor (EGF) receptor phosphorylation and dephosphorylation were studied in normal and growth-retarded fetal rats. Insulin receptor autophosphorylation at a subsaturating ATP concentration (0.5 microM) increased by 10-fold from day 17 to 21 of gestation and decreased by 50% in term growth-retarded fetuses of fasted mothers. In vitro kinase activation at 0.5 mM ATP did not change with gestation or maternal fasting. EGF receptor autophosphorylation increased in parallel with receptor number with advancing gestation and did not change with maternal fasting. Protein tyrosine phosphatases (PTPases), which might attenuate receptor signaling in livers from growth-retarded fetuses, were measured using polybasic and polyacidic artificial substrates as well as the insulin receptor kinase domain. Fetal membrane PTPase activities were twofold higher than in the adult and declined with advancing gestation. However, activities were similar in normal and growth-retarded fetuses. We conclude that decreased hepatic growth in growth-retarded fetuses may involve decreased insulin receptor tyrosine kinase activation in vivo, as indicated by diminished receptor autophosphorylation at subsaturating ATP concentrations. Changes in EGF receptor kinase activity and PTPases could not be implicated based on our in vitro findings.
Gruppuso
P A
PA
Department of Pediatrics, Brown University, Providence, Rhode Island.
Boylan
J M
JM
Carter
P A
PA
Madden
J A
JA
Raven
T
T
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats / Q000196:embryology; D011919:Rats, Inbred Strains; D012016:Reference Values
D007328:Insulin; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases