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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
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D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology; D066246:ErbB Receptors / Q000276:immunology / Q000502:physiology; D020690:GTPase-Activating Proteins; D007421:Intestine, Small / Q000737:chemistry / Q000201:enzymology* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000032:analysis / Q000502:physiology; D011233:Precipitin Tests; D011506:Proteins / Q000032:analysis / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D014886:Weaning; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D066246:ErbB Receptors; D010738:Type C Phospholipases