A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1196581
Author(s) Tremmel, Martina; Matzke, Alexandra; Albrecht, Imke; Laib, Anna M; Olaku, Vivienne; Ballmer-Hofer, Kurt; Christofori, Gerhard; Héroult, Mélanie; Augustin, Hellmut G; Ponta, Helmut; Orian-Rousseau, Véronique
Author(s) at UniBasel Christofori, Gerhard M.
Year 2009
Title A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis
Journal Blood : the journal of the American Society of Hematology
Volume 114
Number 25
Pages / Article-Number 5236-44
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.
Publisher HighWire Press
ISSN/ISBN 1528-0020
edoc-URL http://edoc.unibas.ch/dok/A6006746
Full Text on edoc No
Digital Object Identifier DOI 10.1182/blood-2009-04-219204
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/19773544
ISI-Number WOS:000272612100016
Document type (ISI) Journal Article

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