COFILIN PHOSPHORYLATION BY LIM-KINASE-1 AND ITS ROLE IN RAC-MEDIATED ACTIN REORGANIZATION

Rac is a small GTPase of the Rho family that mediates stimulus-induced actin cytoskeletal reorganization to generate lamellipodia(1-5). Litt le is known about the signalling pathways that link pac activation to changes in actin filament dynamics. Cofilin is known to be a potent re gulator of actin filament dynamics(6-10), and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue a t 3 (refs 11, 12); however, the kinases responsible for this phosphory lation have not been identified. Here we show that LIM-kinase 1 (LIMK- 1), a serine/threonine kinase containing LIM and PDZ domains(13-16), p hosphorylates cofilin at Ser3, both in vitro and in vivo. When express ed in cultured cells, LIMK-1 induces actin reorganization and reverses cofilin-induced actin depolymerization. Expression of an inactive for m of LIMK-1 suppresses lamellipodium formation induced by pac or insul in. Furthermore, insulin and an active form of Rac increase the activi ty of LIMK-1. Taken together, our results indicate that LIMK-1 partici pates in,Rac-mediated actin cytoskeletal reorganization, probably by p hosphorylating cofilin.