A protein kinase from neutrophils that specifically recognizes Ser-3 in cofilin

Cofilin promotes the depolymerization of actin filaments, which is required for a variety of cellular responses such as the formation of lamellipodia and chemotaxis. Phosphorylation of cofilin on serine residue 3 is known to block these activities. We now report that neutrophils contain a protein ki nase that selectively catalyzes the phosphorylation of cofilin on serine 3 (greater than or equal to 70%) and a nonspecific kinase that recognizes mul tiple sites in this protein. The selective serine 3 cofilin kinase binds to a deoxyribonuclease I affinity column, whereas the nonspecific cofilin kin ase does not. Deoxyribonuclease I forms a very tight complex with actin, an d deoxyribonuclease affinity columns have been utilized to identify a varie ty of proteins that interact with the cytoskeleton. The serine 3 cofilin ki nase did not react with antibodies to LIM kinase 1 or 2, which can catalyze the phosphorylation of cofilin in other cell types. The activity of the se rine 3 cofilin kinase was insensitive to a variety of selective antagonists of protein kinases but was blocked by staurosporine. This pattern of inhib ition is similar to that observed for the kinase that is active with cofili n in intact neutrophils. Thus, neutrophils contain a protein kinase distinc t from LIM kinase-1/2 that selectively recognizes serine 3 in cofilin.