Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.
The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.
Maekawa
M
M
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.
Ishizaki
T
T
Boku
S
S
Watanabe
N
N
Fujita
A
A
Iwamatsu
A
A
Obinata
T
T
Ohashi
K
K
Mizuno
K
K
Narumiya
S
S
D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D054461:Lim Kinases; D008246:Lysophospholipids / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases; D020743:rhoB GTP-Binding Protein
D051339:Actin Depolymerizing Factors; D000199:Actins; D000577:Amides; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011725:Pyridines; C108830:Y 27632; D011494:Protein Kinases; C515892:LIMK1 protein, human; C102895:LIMK2 protein, human; D054461:Lim Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020743:rhoB GTP-Binding Protein