PMID- 27363897
OWN - NLM
STAT- MEDLINE
DCOM- 20180508
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jul 1
TI  - Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear 
      export and degradation of p21Cip1.
PG  - 28687
LID - 10.1038/srep28687 [doi]
LID - 28687
AB  - Monocyte chemotactic protein 1 (MCP1) stimulates phosphorylation of cortactin on 
      Y421 and Y446 residues in a time-dependent manner and phosphorylation at Y446 but 
      not Y421 residue is required for MCP1-induced CDK-interacting protein 1 (p21Cip1) 
      nuclear export and degradation in facilitating human aortic smooth muscle cell 
      (HASMC) proliferation. In addition, MCP1-induced cortactin tyrosine 
      phosphorylation, p21Cip1 degradation and HASMC proliferation are dependent on Fyn 
      activation. Upstream to Fyn, MCP1 stimulated C-C chemokine receptor type 2 (CCR2) 
      and Gi/o and inhibition of either one of these molecules using their specific 
      antagonists or inhibitors attenuated MCP1-induced cortactin tyrosine 
      phosphorylation, p21Cip1 degradation and HASMC proliferation. Cortactin 
      phosphorylation at Y446 residue is also required for another G protein-coupled 
      receptor (GPCR) agonist, thrombin-induced p21Cip1 nuclear export and its 
      degradation in promoting HASMC proliferation. Quite interestingly, the receptor 
      tyrosine kinase (RTK) agonist, platelet-derived growth factor-BB 
      (PDGF-BB)-induced p21Cip1 degradation and HASMC proliferation do not require 
      cortactin tyrosine phosphorylation. Together, these findings demonstrate that 
      tyrosine phosphorylation of cortactin at Y446 residue is selective for only GPCR 
      but not RTK agonist-induced nuclear export and proteolytic degradation of p21Cip1 
      in HASMC proliferation.
FAU - Janjanam, Jagadeesh
AU  - Janjanam J
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      TN 38163, USA.
FAU - Rao, Gadiparthi N
AU  - Rao GN
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      TN 38163, USA.
LA  - eng
GR  - R01 HL069908/HL/NHLBI NIH HHS/United States
GR  - R01 HL103575/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160701
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cortactin)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Cell Nucleus/drug effects/*metabolism
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/pharmacology
MH  - Cortactin/genetics/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - Muscle, Smooth, Vascular/cytology
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - Phosphorylation/drug effects
MH  - Proteolysis/drug effects
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Tyrosine/genetics/metabolism
PMC - PMC4929470
EDAT- 2016/07/02 06:00
MHDA- 2018/05/09 06:00
PMCR- 2016/07/01
CRDT- 2016/07/02 06:00
PHST- 2016/02/11 00:00 [received]
PHST- 2016/06/08 00:00 [accepted]
PHST- 2016/07/02 06:00 [entrez]
PHST- 2016/07/02 06:00 [pubmed]
PHST- 2018/05/09 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - srep28687 [pii]
AID - 10.1038/srep28687 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jul 1;6:28687. doi: 10.1038/srep28687.