Activated type I phosphatidylinositol kinase is associated with the epidermal growth factor (EGF) receptor following EGF stimulation.
We have shown that a type I phosphatidylinositol (PI) kinase activity is associated with the epidermal growth factor (EGF) receptor in a mouse fibroblast cell line expressing human EGF receptors (NRHER5) and that this activity increases dramatically upon treatment of cells with physiologically relevant concentrations of EGF. EGF stimulated a time-dependent increase in EGF receptor-associated PI kinase activity measured in EGF receptor immunoprecipitates. Activation was detected 15 min after the addition of EGF, and it peaked between 1 and 2 hr. Activation of PI kinase was detected with EGF concentrations as low as 10 pM and maximal stimulation occurred at approximately 1 nM. Analysis of deacylated PI phosphate products, and inhibition of the PI kinase activity by nonionic detergent, indicated that the PI kinase described here was type I or PI 3' kinase. These results demonstrate the regulation of a type I PI kinase by EGF and suggest a potential role in the EGF receptor signal transduction pathway.
Bjorge
J D
JD
Department of Medical Biochemistry, University of Calgary, Canada.
Chan
T O
TO
Antczak
M
M
Kung
H J
HJ
Fujita
D J
DJ
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D000906:Antibodies; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D010770:Phosphotransferases / Q000378:metabolism*; D014162:Transfection
D000906:Antibodies; D007527:Isoenzymes; D004815:Epidermal Growth Factor; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D066246:ErbB Receptors