Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2

Sutapa Sinha, Pawan Kumar Vohra, Resham Bhattacharya, Shamit Dutta, Shirshendu Sinha, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF)-induced receptor phosphorylation is the crucial step for initiating downstream signaling pathways that lead to angiogenesis or related pathophysiological outcomes. Our previous studies have shown that the neurotransmitter dopamine could inhibit VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), endothelial cell proliferation, migration, microvascular permeability, and thus, angiogenesis. In this study, we address the mechanism by which VEGFR-2 phosphorylation is regulated by dopamine. Here, we demonstrate that D2 dopamine receptor (D2DR) colocalizes with VEGFR-2 at the cell surface. Dopamine pretreatment increases the translocation and colocalization of Src-homology-2-domain-containing protein tyrosine phosphatase (SHP-2) with D2DR at the cell surface. Dopamine administration leads to increased VEGF-induced phosphorylation of SHP-2 and this increased phosphorylation parallels the increased phosphatase activity of SHP-2. Active SHP-2 then dephosphorylates VEGFR-2 at Y951, Y996 and Y1059, but not Y1175. We also observe that SHP-2 knockdown impairs the dopamine-regulated inhibition of VEGF-induced phosphorylation of VEGFR-2 and, subsequently, Src phosphorylation and migration. Our data establish a novel role for SHP-2 phosphatase in the dopamine-mediated regulation of VEGFR-2 phosphorylation.

Original languageEnglish (US)
Pages (from-to)3385-3392
Number of pages8
JournalJournal of cell science
Volume122
Issue number18
DOIs
StatePublished - Sep 15 2009

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Keywords

  • Angiogenesis
  • Dopamine
  • Dopamine D2-receptor (D2DR)
  • Migration
  • Phosphorylation
  • SHP-2
  • Vascular endothelial growth factor receptor 2 (VEGFR-2)

ASJC Scopus subject areas

  • Cell Biology

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