Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho.
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.
Matsui
T
T
Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma, Japan.
Amano
M
M
Yamamoto
T
T
Chihara
K
K
Nakafuku
M
M
Ito
M
M
Nakano
T
T
Okawa
K
K
Iwamatsu
A
A
Kaibuchi
K
K
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
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