Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting

Resham Bhattacharya, Junhye Kwon, Xiujuan Li, Enfeng Wang, Sujata Patra, John Paul Bida, Zeijko Bajzer, Lena Claesson-Welsh, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Endothelial cell proliferation and migration is essential to angiogenesis. Typically, proliferation and chemotaxis of endothelial cells is driven by growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF activates phospholipases (PLCs) - specifically PLCγ1 - that are important for tubulogenesis, differentiation and DNA synthesis. However, we show here that VEGF, specifically through VEGFR2, induces phosphorylation of two serine residues on PLCβ3, and this was confirmed in an ex vivo embryoid body model. Knockdown of PLCβ3 in HUVEC cells affects IP3 production, actin reorganization, migration and proliferation; whereas migration is inhibited, proliferation is enhanced. Our data suggest that enhanced proliferation is precipitated by an accelerated cell cycle, and decreased migration by an inability to activate CDC42. Given that PLCβ3 is typically known as an effector of heterotrimeric G-proteins, our data demonstrate a unique crosstalk between the G-protein and receptor tyrosine kinase (RTK) axes and reveal a novel molecular mechanism of VEGF signaling and, thus, angiogenesis.

Original languageEnglish (US)
Pages (from-to)1025-1034
Number of pages10
JournalJournal of Cell Science
Volume122
Issue number7
DOIs
StatePublished - Apr 1 2009

Fingerprint

Vascular Endothelial Growth Factor A
Blood Vessels
Endothelial Cells
Embryoid Bodies
Heterotrimeric GTP-Binding Proteins
Phospholipases
Human Umbilical Vein Endothelial Cells
Fibroblast Growth Factor 2
Chemotaxis
GTP-Binding Proteins
Protein-Tyrosine Kinases
Serine
Cell Movement
Actins
Intercellular Signaling Peptides and Proteins
Cell Cycle
Phosphorylation
Cell Proliferation
DNA

Keywords

  • Endothelial signaling
  • Migration
  • PLCβ3
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting. / Bhattacharya, Resham; Kwon, Junhye; Li, Xiujuan; Wang, Enfeng; Patra, Sujata; Bida, John Paul; Bajzer, Zeijko; Claesson-Welsh, Lena; Mukhopadhyay, Debabrata.

In: Journal of Cell Science, Vol. 122, No. 7, 01.04.2009, p. 1025-1034.

Research output: Contribution to journalArticle

Bhattacharya, R, Kwon, J, Li, X, Wang, E, Patra, S, Bida, JP, Bajzer, Z, Claesson-Welsh, L & Mukhopadhyay, D 2009, 'Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting', Journal of Cell Science, vol. 122, no. 7, pp. 1025-1034. https://doi.org/10.1242/jcs.041913
Bhattacharya R, Kwon J, Li X, Wang E, Patra S, Bida JP et al. Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting. Journal of Cell Science. 2009 Apr 1;122(7):1025-1034. https://doi.org/10.1242/jcs.041913
Bhattacharya, Resham ; Kwon, Junhye ; Li, Xiujuan ; Wang, Enfeng ; Patra, Sujata ; Bida, John Paul ; Bajzer, Zeijko ; Claesson-Welsh, Lena ; Mukhopadhyay, Debabrata. / Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting. In: Journal of Cell Science. 2009 ; Vol. 122, No. 7. pp. 1025-1034.
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