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 Citations (Scopus)

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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SH2 Domain-Containing Protein Tyrosine Phosphatases
Protein Phosphatase 2
Vascular Endothelial Growth Factor Receptor-2
Protein Tyrosine Phosphatases
Vascular Endothelial Growth Factor Receptor
Dopamine
Phosphorylation
Vascular Endothelial Growth Factor A
Dopamine D2 Receptors
Phosphoric Monoester Hydrolases
Capillary Permeability
Cell Movement
Neurotransmitter Agents
Endothelial Cells
Cell Proliferation

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

Cite this

Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2. / Sinha, Sutapa; Vohra, Pawan Kumar; Bhattacharya, Resham; Dutta, Shamit; Sinha, Shirshendu; Mukhopadhyay, Debabrata.

In: Journal of Cell Science, Vol. 122, No. 18, 15.09.2009, p. 3385-3392.

Research output: Contribution to journalArticle

Sinha, Sutapa ; Vohra, Pawan Kumar ; Bhattacharya, Resham ; Dutta, Shamit ; Sinha, Shirshendu ; Mukhopadhyay, Debabrata. / Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2. In: Journal of Cell Science. 2009 ; Vol. 122, No. 18. pp. 3385-3392.
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