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
%0 Journal Article
%1 Gampel.2006
%A Gampel, A.
%A Moss, L.
%A Jones, M. C.
%A Brunton, V.
%A Norman, J. C.
%A Mellor, H.
%D 2006
%J Blood
%K A Active Adult Biological Blood Cell Cells Compartmentation Cultured Endosomes Endothelial Factor GTP-Binding Growth Humans Kinases Laboratories Lysosomes Membrane Plasma Proteins Receptor-2 Recombinant Research Transport Tyrosine Vascular Vessels blood cells cytology drug effects metabolism pharmacology protein rab4 response src-Family
%N 8
%P 2624-2631
%T VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment
%U PM:16638931
%V 108
%X 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
@article{Gampel.2006,
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 },
added-at = {2010-02-05T11:28:39.000+0100},
author = {Gampel, A. and Moss, L. and Jones, M. C. and Brunton, V. and Norman, J. C. and Mellor, H.},
biburl = {https://www.bibsonomy.org/bibtex/2cb4326c220a7ae5391331cd9d57f2d46/kanefendt},
interhash = {eff205344ee2b9f4b309cc95e9cdd7f4},
intrahash = {cb4326c220a7ae5391331cd9d57f2d46},
journal = {Blood},
keywords = {A Active Adult Biological Blood Cell Cells Compartmentation Cultured Endosomes Endothelial Factor GTP-Binding Growth Humans Kinases Laboratories Lysosomes Membrane Plasma Proteins Receptor-2 Recombinant Research Transport Tyrosine Vascular Vessels blood cells cytology drug effects metabolism pharmacology protein rab4 response src-Family},
number = 8,
pages = {2624-2631},
timestamp = {2010-02-05T11:28:54.000+0100},
title = {VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment},
url = {PM:16638931},
volume = 108,
year = 2006
}