Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase

An epidermal-growth-factor(EGF)-receptor preparation isolated by calmodulin-affinity chroma-tography from rat liver plasma membranes is able to phosphorylate calmodulin. Calmodulin phos-phorylation 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 3ZP/calmodulin molar ratio of approxi-mately 1 when optimal phosphorylation conditions are used. Calmodulin is an intracellular calcium receptor that me-diates multiple essential functions in eukaryotic cells (Mean