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A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis

Tremmel, Martina and Matzke, Alexandra and Albrecht, Imke and Laib, Anna M. and Olaku, Vivienne and Ballmer-Hofer, Kurt and Christofori, Gerhard and Héroult, Mélanie and Augustin, Hellmut G. and Ponta, Helmut and Orian-Rousseau, Véronique. (2009) A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis. Blood : the journal of the American Society of Hematology, Vol. 114. pp. 5236-5244.

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Official URL: http://edoc.unibas.ch/dok/A6006746

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Abstract

A specific splice variant of the CD44 cell- surface protein family, CD44v6, has been shown to act as a coreceptor for the receptor tyrosine kinase c-Met on epithelial cells. Here we show that also on endothelial cells (ECs), the activity of c-Met is dependent on CD44v6. Furthermore, another receptor tyrosine kinase, VEGFR-2, is also regulated by CD44v6. The CD44v6 ectodomain and a small peptide mimicking a specific extracellular motif of CD44v6 or a CD44v6-specific antibody prevent CD44v6-mediated receptor activation. This indicates that the extracellular part of CD44v6 is required for interaction with c-Met or VEGFR-2. In the cytoplasm, signaling by activated c-Met and VEGFR-2 requires association of the CD44 carboxy-terminus with ezrin that couples CD44v6 to the cytoskeleton. CD44v6 controls EC migration, sprouting, and tubule formation induced by hepatocyte growth factor (HGF) or VEGF-A. In vivo the development of blood vessels from grafted EC spheroids and angiogenesis in tumors is impaired by CD44v6 blocking reagents, suggesting that the coreceptor function of CD44v6 for c-Met and VEGFR-2 is a promising target to block angiogenesis in pathologic conditions.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:HighWire Press
ISSN:1528-0020
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:41

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