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. Little is known about the signalling pathways that link Rac activation to changes in actin filament dynamics. Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3; however, the kinases responsible for this phosphorylation have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a serine/threonine kinase containing LIM and PDZ domains, phosphorylates cofilin at Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1 induces actin reorganization and reverses cofilin-induced actin depolymerization. Expression of an inactive form of LIMK-1 suppresses lamellipodium formation induced by Rac or insulin. Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin.
Yang
N
N
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Higuchi
O
O
Ohashi
K
K
Nagata
K
K
Wada
A
A
Kangawa
K
K
Nishida
E
E
Mizuno
K
K
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D020744:rac GTP-Binding Proteins
D051339:Actin Depolymerizing Factors; D000199:Actins; D004268:DNA-Binding Proteins; D007328:Insulin; D008840:Microfilament Proteins; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515894:Limk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins