title: Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho.
abstract: The small GTP binding protein Rho is implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid to form stress fibers and focal contacts. Here we have purified a Rho-interacting protein with a molecular mass of approximately 164 kDa (p164) from bovine brain. This protein bound to GTPgammaS (a non-hydrolyzable GTP analog).RhoA but not to GDP.RhoA or GTPgammaS.RhoA with a mutation in the effector domain (RhoAA37).p164 had a kinase activity which was specifically stimulated by GTPgammaS.RhoA. We obtained the cDNA encoding p164 on the basis of its partial amino acid sequences and named it Rho-associated kinase (Rho-kinase). Rho-kinase has a catalytic domain in the N-terminal portion, a coiled coil domain in the middle portion and a zinc finger-like motif in the C-terminal portion. The catalytic domain shares 72% sequence homology with that of myotonic dystrophy kinase and the coiled coil domain contains a Rho-interacting interface. When COS7 cells were cotransfected with Rho-kinase and activated RhoA, some Rho-kinase was recruited to membranes. Thus it is likely that Rho-kinase is a putative target serine/threonine kinase for Rho and serves as a mediator of the Rho-dependent signaling pathway.
authors.affiliation: Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: M
authors.initials: M
authors.lastname: Amano
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Chihara
authors.forename: M
authors.initials: M
authors.lastname: Nakafuku
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Okawa
authors.forename: A
authors.initials: A
authors.lastname: Iwamatsu
authors.forename: K
authors.initials: K
authors.lastname: Kaibuchi
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002417:Cattle; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D054460:rho-Associated Kinases
chemical_list: C585516:DMPK protein, mouse; D017931:DNA Primers; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019204:GTP-Binding Proteins