PMID- 11278464
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20220227
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 19
DP  - 2001 May 11
TI  - Distinct signaling pathways for MCP-1-dependent integrin activation and 
      chemotaxis.
PG  - 16555-60
AB  - Transmigration of monocytes to the subendothelial space is the initial step of 
      atherosclerotic plaque formation and inflammation. Integrin activation and 
      chemotaxis are two important functions involved in monocyte transmigration. To 
      delineate the signaling cascades leading to integrin activation and chemotaxis by 
      monocyte chemoattractant protein-1 (MCP-1), we have investigated the roles of 
      MAPK and Rho GTPases in THP-1 cells, a monocytic cell line. MCP-1 stimulated 
      beta1 integrin-dependent, but not beta2 integrin-dependent cell adhesion in a 
      time-dependent manner. MCP-1-mediated cell adhesion was inhibited by a MEK 
      inhibitor but not by a p38-MAPK inhibitor. In contrast, MCP-1-mediated chemotaxis 
      was inhibited by the p38-MAPK inhibitor but not by the MEK inhibitor. The 
      inhibitor of Rho GTPase, C3 exoenzyme, and a Rho kinase inhibitor abrogated 
      MCP-1-dependent chemotaxis but not integrin-dependent cell adhesion. Further, C3 
      exoenzyme and the Rho kinase inhibitor blocked MCP-1-dependent p38-MAPK 
      activation. These data indicate that ERK is responsible for integrin activation, 
      that p38-MAPK and Rho are responsible for chemotaxis mediated by MCP-1, and that 
      Rho and the Rho kinase are upstream of p38-MAPK in MCP-1-mediated signaling. This 
      study demonstrates that two distinct MAPKs regulate two dependent signaling 
      cascades leading to integrin activation and chemotaxis induced by MCP-1 in THP-1 
      cells.
FAU - Ashida, N
AU  - Ashida N
AD  - Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, 
      Kyoto, 606-8507, Japan.
FAU - Arai, H
AU  - Arai H
FAU - Yamasaki, M
AU  - Yamasaki M
FAU - Kita, T
AU  - Kita T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010207
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CD18 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fibronectins)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Integrin beta1)
RN  - 0 (Pyridines)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - CD18 Antigens/*physiology
MH  - Cell Adhesion/drug effects/*physiology
MH  - Cell Line
MH  - Chemokine CCL2/*pharmacology
MH  - Chemotaxis, Leukocyte/drug effects/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibronectins/physiology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Integrin beta1/*physiology
MH  - Kinetics
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Monocytes
MH  - Pyridines/pharmacology
MH  - Signal Transduction/*physiology
MH  - Vascular Cell Adhesion Molecule-1/physiology
MH  - p38 Mitogen-Activated Protein Kinases
MH  - rho GTP-Binding Proteins/metabolism
EDAT- 2001/03/30 10:00
MHDA- 2001/06/15 10:01
CRDT- 2001/03/30 10:00
PHST- 2001/03/30 10:00 [pubmed]
PHST- 2001/06/15 10:01 [medline]
PHST- 2001/03/30 10:00 [entrez]
AID - S0021-9258(19)32090-3 [pii]
AID - 10.1074/jbc.M009068200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 May 11;276(19):16555-60. doi: 10.1074/jbc.M009068200. Epub 2001 
      Feb 7.