Ontogenic regulation of phospholipase C-γ1 activity and expression in the rat small intestine

Abstract

Background/Aims: The postnatal rat small intestine undergoes major morphological, biochemical, and physiological changes during weaning. Phospholipase C-γ1 (PLCγ1), 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 PLCγ1 expression, catalytic activity, and growth factor regulation of PLCγ1. Methods: Immunodetection was used to compare the expression and tyrosine phosphorylation state of PLCγ1, EGFR, phosphatidylinositol 3-kinase (PI 3-kinase), ras guanosine triphosphatase activating protein (GAP), and src homologous collagenlike protein (SHC) in the postnatal rat intestine. Results:The catalytic activity and expression of PLCγ1 markedly increased during weaning. Significant EGF-induced increases in the activity and tyrosine phosphorylation of PLCγ1 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. Conclusions: The expression and catalytic activity of rat intestinal PLCγ1 are greatest during weaning. A functional consequence is the age-dependent modulation of EGF regulation of PLCγ1 tyrosine phosphorylation state and catalytic activity. This is the first in vivo demonstration of EGF-dependent tyrosine phosphorylation of PLCγ1 in normal animal tissue.