Rho-associated Kinase ROCK Activates LIM-kinase 1 by Phosphorylation at Threonine 508 within the Activation Loop

作者: Kazumasa Ohashi , Kyoko Nagata , Midori Maekawa , Toshimasa Ishizaki , Shuh Narumiya

DOI: 10.1074/JBC.275.5.3577

关键词: PhosphorylationMAP2K7Protein phosphorylationSerine/threonine-specific protein kinaseProtein kinase AChemistryCell biologyMolecular biologyPAK1Lim kinaseKinase activityBiochemistry

摘要: LIM-kinase 1 (LIMK1) phosphorylates cofilin, an actin-depolymerizing factor, and regulates actin cytoskeletal reorganization. LIMK1 is activated by the small GTPase Rho its downstream protein kinase ROCK. We now report site of phosphorylation In vitro reaction revealed that active forms ROCK phosphorylated on threonine residue markedly increased cofilin-phosphorylating activity. A mutant (T508A) with replacement Thr-508 within activation loop domain alanine was neither nor Replacement serine changed ROCK-catalyzed from to serine. two glutamates activity about 2-fold but not further addition, wild-type LIMK1, T508A mutant, co-expression in cultured cells. These results suggest activates vivo at Thr-508. Together recent finding PAK1, a effector Rac, also Thr-508, these one common targets for Rac reorganize cytoskeleton.

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