Ontogenic regulation of phospholipase C-gamma 1 activity and expression in the rat small intestine.

Abstract

The postnatal rat small intestine undergoes major morphological, biochemical, and physiological changes during weaning. Phospholipase C-gamma 1 (PLC gamma 1), a tyrosine kinase substrate of the epidermal growth factor receptor (EGFR) hydrolyzes phosphatidylinositol-4,5-bisphosphate to products that may serve as mediators of growth and development. The aim of this study was to define developmental changes in intestinal PLC gamma 1 expression, catalytic activity, and growth factor regulation of PLC gamma 1. Immunodetection was used to compare the expression and tyrosine phosphorylation state of PLC gamma 1, EGFR, phosphatidylinositol 3-kinase (PI 3-kinase), ras guanosine triphosphatase activating protein (GAP), and src homologous collagen-like protein (SHC) in the postnatal rat intestine. The catalytic activity and expression of PLC gamma 1 markedly increased during weaning. Significant EGF-induced increases in the activity and tyrosine phosphorylation of PLC gamma 1 occurred in weanling but not suckling animals. EGFR and SHC expression were increased in weanling compared with suckling and adult animals; however, differences in expression of PI 3-kinase and GAP did not occur during weaning. The expression and catalytic activity of rat intestinal PLC gamma 1 are greatest during weaning. A functional consequence is the age-dependent modulation of EGF regulation of PLC gamma 1 tyrosine phosphorylation state and catalytic activity. This is the first in vivo demonstration of EGF-dependent tyrosine phosphorylation of PLC gamma 1 in normal animal tissue.