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Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1

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 ao...

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Autores principales: Janjanam, Jagadeesh, Rao, Gadiparthi N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929470/
https://www.ncbi.nlm.nih.gov/pubmed/27363897
http://dx.doi.org/10.1038/srep28687
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author Janjanam, Jagadeesh
Rao, Gadiparthi N.
author_facet Janjanam, Jagadeesh
Rao, Gadiparthi N.
author_sort Janjanam, Jagadeesh
collection PubMed
description 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.
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spelling pubmed-49294702016-07-06 Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1 Janjanam, Jagadeesh Rao, Gadiparthi N. Sci Rep Article 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. Nature Publishing Group 2016-07-01 /pmc/articles/PMC4929470/ /pubmed/27363897 http://dx.doi.org/10.1038/srep28687 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Janjanam, Jagadeesh
Rao, Gadiparthi N.
Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1
title Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1
title_full Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1
title_fullStr Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1
title_full_unstemmed Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1
title_short Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1
title_sort novel role of cortactin in g protein-coupled receptor agonist-induced nuclear export and degradation of p21cip1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929470/
https://www.ncbi.nlm.nih.gov/pubmed/27363897
http://dx.doi.org/10.1038/srep28687
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