Calmodulin Activates

Calmodulin and phosphatidylinositol 3-kinase are vi-tal components of a number of common intracellular events. Calmodulin, a ubiquitous Ca21-dependent effec-tor protein, regulates multiple processes in eukaryotic cells, including cytoskeletal organization, vesicular traf-ficking, and mitogenesis. Phosphatidylinositol 3-kinase participates in events downstream of the receptors for insulin and other growth factors. Here we demonstrate by coimmunoprecipitation and affinity chromatography that Ca21/calmodulin associates with Src homology 2 do-mains in the 85-kDa regulatory subunit of phosphatidyl-inositol 3-kinase, thereby significantly enhancing phos-phatidylinositol 3-kinase activity in vitro and in intact cells. Furthermore, CGS9343B, a calmodulin antagonist, inhibited basal and Ca21-stimulated phosphorylation o