EPIDERMAL GROWTH-FACTOR RECEPTOR ACTIVATION IN DEVELOPING RAT-KIDNEY

Epidermal growth factor (EGF) binding increases in late-gestational ra t kidney and then falls toward basal adult levels postnatally during t he 1st wk. We report that the increase in EGF binding is accompanied b y an increase in EGF receptor (EGFR) protein and activation of EGFR ty rosine kinase. Multiple proteins were endogenously tyrosine phosphoryl ated in kidney membranes from fetal rats, and the phosphorylation patt ern was similar in rats ranging from 16 to 21 days of gestation. Tyros ine phosphorylation was, however, almost undetectable in 12-wk adult r at kidneys (controls). Among the phosphoproteins in fetal kidney, a pr ominent 170-kDa protein was identified as EGFR. Endogenous tyrosine ph osphorylation of EGFR (reflecting receptor activation) was 30-fold hig her in fetal kidney membranes than in adult (3- to 7-fold higher when adjusted for differences in EGF binding or EGFR protein content). The EGFR substrate, phospholipase C-(gamma 1), was tyrosine phosphorylated in fetal kidneys but not adult, and a greater proportion was membrane -associated in fetal kidneys, consistent with activation of phospholip ase C-(gamma 1). Thus EGFR tyrosine kinase activity is increased in la te-gestational rat kidney. Induction and activation of EGFR may mediat e perinatal renal cell growth and development.