PMID- 26490115
OWN - NLM
STAT- MEDLINE
DCOM- 20160926
LR  - 20181113
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 26
IP  - 25
DP  - 2015 Dec 15
TI  - PLCbeta3 mediates cortactin interaction with WAVE2 in MCP1-induced actin 
      polymerization and cell migration.
PG  - 4589-606
LID - 10.1091/mbc.E15-08-0570 [doi]
AB  - Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell 
      (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying 
      MCP1-induced VSMC migration have not been understood. Here we identify the 
      signaling pathway associated with MCP1-induced human aortic smooth muscle cell 
      (HASMC) migration. MCP1, a G protein-coupled receptor agonist, activates 
      phosphorylation of cortactin on S405 and S418 residues in a time-dependent 
      manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC 
      G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin 
      phosphorylation on S405/S418 is found to be critical for its interaction with 
      WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required 
      for cell migration. In addition, the MCP1-induced cortactin phosphorylation is 
      dependent on PLCbeta3-mediated PKCdelta activation, and siRNA-mediated down-regulation 
      of either of these molecules prevents cortactin interaction with WAVE2, affecting 
      G-actin polymerization, F-actin stress fiber formation, and HASMC migration. 
      Upstream, MCP1 activates CCR2 and Galphaq/11 in a time-dependent manner, and 
      down-regulation of their levels attenuates MCP1-induced PLCbeta3 and PKCdelta 
      activation, cortactin phosphorylation, cortactin-WAVE2 interaction, G-actin 
      polymerization, F-actin stress fiber formation, and HASMC migration. Together 
      these findings demonstrate that phosphorylation of cortactin on S405 and S418 
      residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton 
      remodeling, facilitating HASMC migration.
CI  - (c) 2015 Janjanam et al. This article is distributed by The American Society for 
      Cell Biology under license from the author(s). Two months after publication it is 
      available to the public under an Attribution-Noncommercial-Share Alike 3.0 
      Unported Creative Commons License 
      (http://creativecommons.org/licenses/by-nc-sa/3.0).
FAU - Janjanam, Jagadeesh
AU  - Janjanam J
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      TN 38163.
FAU - Chandaka, Giri Kumar
AU  - Chandaka GK
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      TN 38163.
FAU - Kotla, Sivareddy
AU  - Kotla S
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      TN 38163.
FAU - Rao, Gadiparthi N
AU  - Rao GN
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      TN 38163 rgadipar@uthsc.edu.
LA  - eng
GR  - R01 HL069908/HL/NHLBI NIH HHS/United States
GR  - R01 HL103575/HL/NHLBI NIH HHS/United States
GR  - HL069908/HL/NHLBI NIH HHS/United States
GR  - HL103575/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151021
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Actins)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cortactin)
RN  - 0 (WASF2 protein, human)
RN  - 0 (Wiskott-Aldrich Syndrome Protein Family)
RN  - EC 3.1.4.11 (PLCB3 protein, human)
RN  - EC 3.1.4.11 (Phospholipase C beta)
SB  - IM
MH  - Actins/genetics/metabolism
MH  - Aorta/growth & development/metabolism
MH  - Cell Movement/*genetics
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Cortactin/genetics/*metabolism
MH  - Cytoskeleton/genetics/metabolism
MH  - Humans
MH  - Muscle Fibers, Skeletal/metabolism
MH  - Muscle, Smooth, Vascular/*growth & development/metabolism
MH  - Phospholipase C beta/genetics/*metabolism
MH  - Phosphorylation
MH  - Wiskott-Aldrich Syndrome Protein Family/metabolism
PMC - PMC4678017
EDAT- 2015/10/23 06:00
MHDA- 2016/09/27 06:00
PMCR- 2016/03/01
CRDT- 2015/10/23 06:00
PHST- 2015/08/11 00:00 [received]
PHST- 2015/10/13 00:00 [accepted]
PHST- 2015/10/23 06:00 [entrez]
PHST- 2015/10/23 06:00 [pubmed]
PHST- 2016/09/27 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - mbc.E15-08-0570 [pii]
AID - E15-08-0570 [pii]
AID - 10.1091/mbc.E15-08-0570 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2015 Dec 15;26(25):4589-606. doi: 10.1091/mbc.E15-08-0570. Epub 
      2015 Oct 21.