Growth factor phosphorylation of PLC-gamma 1.
The hydrolysis of phosphatidylinositol 4,5-bisphosphate has a central role in many signalling pathways. One of the phospholipase C (PLC) isozymes that mediates this reaction is a direct substrate for the tyrosine kinase activity of several growth factor receptors. Growth factors elicit increases in both the phosphoserine and the phosphotyrosine content of the PLC-gamma 1 isozyme. PLC-gamma 1 contains three tyrosine phosphorylation sites, which have been identified as residues 771, 783 and 1254. Phosphorylation of tyrosine residues is sufficient to increase the catalytic activity of PLC-gamma 1, though other proteins may modulate this activation. However, the role of growth factor-enhanced phosphorylation of serine residues on PLC-gamma 1 remains obscure. In vitro studies of PLC-gamma 1, recovered from growth factor-treated cells, indicate that activation by tyrosine phosphorylation is not due to increased sensitivity to Ca2+, a required co-factor, but is reflected in altered kinetic constants, i.e. V(max) and, to a lesser extent, Km.
Carpenter
G
G
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
Hernández-Sotomayor
S M
SM
Nishibe
S
S
Todderud
G
G
Mumby
M
M
Wahl
M
M
D004789:Enzyme Activation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases