PHOSPHORYLATION OF CALMODULIN BY THE EPIDERMAL-GROWTH-FACTOR-RECEPTOR TYROSINE KINASE

An epidermal-grow th-factor(EGF)-receptor preparation is elated by calmodulin-affinity chromatography from rat liver plasma membranes is able to phosphorylate calmodulin. Calmodulin phosphorylation was enhanced 3-8-fold by EGF, was dependent on the presence of a polycation or basic protein and was inhibited by micromolar concentrations of Ca2+. Phosphate incorporation into calmodulin occurs predominantly on tyrosine residues. Partial proteolysis of phosphocalmodulin by thrombin identifies Tyr99, located in the third calcium-binding domain of calmodulin, as the phosphorylated residue. Stoichiometric measurements show a P-32/calmodulin molar ratio of approximately 1 when optimal phosphorylation conditions are used.