PMID- 25502873
OWN - NLM
STAT- MEDLINE
DCOM- 20150518
LR  - 20171116
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 230
IP  - 6
DP  - 2015 Jun
TI  - Rac1 regulates myosin II phosphorylation through regulation of myosin light chain 
      phosphatase.
PG  - 1352-64
LID - 10.1002/jcp.24878 [doi]
AB  - Phosphorylation of regulatory light chain (MLC) activates myosin II, which 
      enables it to promote contractile and motile activities of cells. We report here 
      a novel signaling mechanism that activates MLC phosphorylation and smooth muscle 
      contraction. Contractile agonists activated Rac1, and Rac1 inhibition diminished 
      agonist-induced MLC phosphorylation, thus inhibiting smooth muscle contraction. 
      Rac1 inhibits the activity of MLC phosphatase (MLCP) but not that of MLC kinase, 
      through a phosphatase that targets MYPT1 (a regulatory subunit of MLCP) and 
      CPI-17 (a MLCP specific inhibitor) rather than through the RhoA-Rho dependent 
      kinase (ROCK) pathway. Rac1 inhibition decreased the activity of protein kinase C 
      (PKC), which also contributes to the change in CPI-17 phosphorylation. We propose 
      that activation of Rac1 increases the activity of PKC, which increases the 
      phosphorylation of CPI-17 and MYPT1 by inhibiting the phosphatase that targets 
      these proteins, thereby decreasing the activity of MLCP and increasing 
      phosphorylation of MLC. Our results suggest that Rac1 coordinates with RhoA to 
      increase MLC phosphorylation by inactivation of CPI-17/MYPT1 phosphatase, which 
      decreases MLCP activity thus promoting MLC phosphorylation and cell contraction.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Shibata, Keita
AU  - Shibata K
AD  - Department of Microbiology and Physiological Systems, University of Massachusetts 
      Medical School, Worcester, Massachusetts.
FAU - Sakai, Hiroyasu
AU  - Sakai H
FAU - Huang, Qian
AU  - Huang Q
FAU - Kamata, Hirotoshi
AU  - Kamata H
FAU - Chiba, Yoshihiko
AU  - Chiba Y
FAU - Misawa, Miwa
AU  - Misawa M
FAU - Ikebe, Reiko
AU  - Ikebe R
FAU - Ikebe, Mitsuo
AU  - Ikebe M
LA  - eng
GR  - HL111696/HL/NHLBI NIH HHS/United States
GR  - HL073050/HL/NHLBI NIH HHS/United States
GR  - HL106461/HL/NHLBI NIH HHS/United States
GR  - R01 HL073050/HL/NHLBI NIH HHS/United States
GR  - R21 HL106461/HL/NHLBI NIH HHS/United States
GR  - R01 HL111696/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Muscle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Ppp1r14a protein, rat)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.3.16 (Ppp1r12a protein, rat)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.53 (Myosin-Light-Chain Phosphatase)
RN  - EC 3.6.1.- (Myosin Type II)
RN  - EC 3.6.1.- (Rac1 protein, rat)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Muscle Contraction/physiology
MH  - Muscle Proteins/*metabolism
MH  - Muscle, Smooth/metabolism
MH  - Myosin Type II/*metabolism
MH  - Myosin-Light-Chain Phosphatase/*metabolism
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Protein Phosphatase 1/*metabolism
MH  - Rats
MH  - rac1 GTP-Binding Protein/*metabolism
MH  - rhoA GTP-Binding Protein/*metabolism
EDAT- 2014/12/17 06:00
MHDA- 2015/05/20 06:00
CRDT- 2014/12/16 06:00
PHST- 2014/09/30 00:00 [received]
PHST- 2014/12/05 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/05/20 06:00 [medline]
AID - 10.1002/jcp.24878 [doi]
PST - ppublish
SO  - J Cell Physiol. 2015 Jun;230(6):1352-64. doi: 10.1002/jcp.24878.