Phosphatidylinositol 4,5-bisphosphate specifically stimulates PP60(c-src) catalyzed phosphorylation of gelsolin and related actin-binding proteins.

Gelsolin is a widely distributed Ca2+-dependent regulator of the cortical actin network. We demonstrate that gelsolin is phosphorylated by pp60(c-src) and that this phosphorylation is dramatically enhanced by phosphatidylinositol 4,5-bisphosphate (PIP2), known to specifically interact with gelsolin. Other phospholipids display only a marginal effect. pp56(lck), a tyrosine kinase of the same family, does not phosphorylate gelsolin. Other mammalian actin-binding proteins such as profilin and CapG but also fragmin from Physarum polycephalum are similar targets for PIP2-stimulated pp60(c-src) phosphorylation.