AJP - Endocrinology and Metabolism, Vol 262, Issue 1 E6-13, Copyright © 1992 by American Physiological Society
Hepatic insulin and EGF receptor phosphorylation and dephosphorylation in fetal rats
P. A. Gruppuso, J. M. Boylan, P. A. Carter, J. A. Madden and T. Raven
Department of Pediatrics, Brown University, Providence, Rhode Island.
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.
