Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho

EMBO J. 1996 May 1;15(9):2208-16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Catalysis
  • Cattle
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Myotonin-Protein Kinase
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins / metabolism
  • Subcellular Fractions / enzymology
  • rho-Associated Kinases

Substances

  • DMPK protein, mouse
  • DNA Primers
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Myotonin-Protein Kinase
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • GTP-Binding Proteins

Associated data

  • GENBANK/U36909