PMID- 10652353
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 5
DP  - 2000 Feb 4
TI  - Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine
      508 within the activation loop.
PG  - 3577-82
AB  - LIM-kinase 1 (LIMK1) phosphorylates cofilin, an actin-depolymerizing factor, and 
      regulates actin cytoskeletal reorganization. LIMK1 is activated by the small
      GTPase Rho and its downstream protein kinase ROCK. We now report the site of
      phosphorylation of LIMK1 by ROCK. In vitro kinase reaction revealed that the
      active forms of ROCK phosphorylated LIMK1 on the threonine residue and markedly
      increased its cofilin-phosphorylating activity. A LIMK1 mutant (T508A) with
      replacement of Thr-508 within the activation loop of the kinase domain by alanine
      was neither phosphorylated nor activated by ROCK. Replacement of Thr-508 by
      serine changed the ROCK-catalyzed phosphorylation residue from threonine to
      serine. A LIMK1 mutant with replacement of Thr-508 by two glutamates increased
      the kinase activity about 2-fold but was not further activated by ROCK. In
      addition, wild-type LIMK1, but not its T508A mutant, was activated by
      co-expression with ROCK in cultured cells. These results suggest that ROCK
      activates LIMK1 in vitro and in vivo by phosphorylation at Thr-508. Together with
      the recent finding that PAK1, a downstream effector of Rac, also activates LIMK1 
      by phosphorylation at Thr-508, these results suggest that activation of LIMK1 is 
      one of the common targets for Rho and Rac to reorganize the actin cytoskeleton.
FAU - Ohashi, K
AU  - Ohashi K
AD  - Biological Institute, Graduate School of Science, Tohoku University, Sendai
      980-8578, Japan.
FAU - Nagata, K
AU  - Nagata K
FAU - Maekawa, M
AU  - Maekawa M
FAU - Ishizaki, T
AU  - Ishizaki T
FAU - Narumiya, S
AU  - Narumiya S
FAU - Mizuno, K
AU  - Mizuno K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Lim Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Enzyme Activation
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lim Kinases
MH  - Mutagenesis, Site-Directed
MH  - Neuroblastoma/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/genetics/*metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Threonine
MH  - rho GTP-Binding Proteins/*metabolism
MH  - rho-Associated Kinases
EDAT- 2000/02/01 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1074/jbc.275.5.3577 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 4;275(5):3577-82. doi: 10.1074/jbc.275.5.3577.