VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment

Alexandra Gampel, Lara Moss, Matt C Jones, Val Brunton, Jim C Norman, Harry Mellor

Research output: Contribution to journalArticle (Academic Journal)

134 Citations (Scopus)

Abstract

Endothelial cells respond to vascular endothelial growth factor (VEGF) to produce new blood vessels. This process of angiogenesis makes a critical contribution during embryogenesis and also in the response to ischemia in adult tissues. We have studied the intracellular trafficking of the major VEGF receptor KDR (VEGFR2). Unlike other related growth factor receptors, we find that a significant proportion of KDR is held in an endosomal storage pool within endothelial cells. We find that KDR can be delivered to the plasma membrane from this intracellular pool and that VEGF stimulates this recycling to the cell surface. KDR recycling appears to be distinct from the previously characterized Rab4- and Rab11-dependent pathways, but, instead, KDR(+) recycling vesicles contain Src tyrosine kinase and VEGF-stimulated recycling requires Src activation. Taken together, these data show that intracellular trafficking of KDR is markedly different from other receptor tyrosine kinases and suggest that the regulation of KDR trafficking by VEGF provides a novel mechanism for controlling the sensitivity of endothelial cells to proangiogenic signals.

Original languageEnglish
Pages (from-to)2624 - 2631
Number of pages8
JournalBlood
Volume108
Issue number8
DOIs
Publication statusPublished - 15 Oct 2006

Bibliographical note

Publisher: American Society of Hematology
Other: L Moss was a final year undergraduate at Bristol

Keywords

  • Biological Transport, Active
  • Cell Compartmentation
  • Cell Membrane
  • Cells, Cultured
  • Endosomes
  • Endothelial Cells
  • Humans
  • Lysosomes
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • rab4 GTP-Binding Proteins
  • src-Family Kinases

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