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

Jagadeesh Janjanam, Rao Gadiparthi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number28687
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 1 2016

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Cortactin
Cell Nucleus Active Transport
G-Protein-Coupled Receptors
Chemokine CCL2
Smooth Muscle Myocytes
Phosphorylation
Cell Proliferation
Tyrosine
Receptor Protein-Tyrosine Kinases
CC Chemokines
Chemokine Receptors
Thrombin

All Science Journal Classification (ASJC) codes

  • General

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Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1. / Janjanam, Jagadeesh; Gadiparthi, Rao.

In: Scientific Reports, Vol. 6, 28687, 01.07.2016.

Research output: Contribution to journalArticle

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