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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2016 (publ. 2015, arch)     Display Documents

ID: 717255.0, MPI für molekulare Biomedizin / Jahrbuch 2016 (publ. 2015, arch)
Regulation of vascular endothelial growth factor receptor function in angiogenesis by numb and numb-like
Authors:van Lessen, M.; Nakayama, M.; Kato, K.; Kim, J. M.; Kaibuchi, K.; Adams, R. H.
Date of Publication (YYYY-MM-DD):2015-08
Title of Journal:Arterioscler Thromb Vasc Biol
Issue / Number:8
Start Page:1815
End Page:1825
Review Status:Internal review
Audience:Not Specified
Abstract / Description:OBJECTIVE: Vascular endothelial growth factor (VEGF) signaling is a major regulator of physiological and pathological angiogenesis. VEGF receptor activity is strongly controlled by endocytosis, which can terminate or enhance signal transduction in the angiogenic endothelium, but the exact molecular regulation of these processes remains incompletely understood. We have therefore examined the function of Numb family clathrin-associated sorting proteins in angiogenesis. APPROACH AND RESULTS: We show that Numb proteins are expressed by endothelial cells during retinal angiogenesis in mice. Inducible inactivation of the Numb/Numbl genes in the postnatal endothelium led to impaired vessel growth, reduced endothelial proliferation and sprouting, and decreased VEGF receptor activation. Biochemistry and cell biology experiments established that Numb can interact with VEGFR2 and VEGFR3 and controls VEGF receptor activation in response to ligand stimulation. Experiments in cultured endothelial cells showed that Numb proteins counteract VEGF receptor degradation and promote VEGFR2 recycling back to the plasma membrane. CONCLUSIONS: Numb proteins control VEGF receptor endocytosis, signaling, and recycling in endothelial cells, which promotes the angiogenic growth of blood vessels.
Free Keywords:Animals; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Endocytosis; Endothelial Cells/*metabolism; Human Umbilical Vein Endothelial Cells/metabolism; Humans; Intracellular Signaling Peptides and Proteins/genetics/*metabolism; Membrane Proteins/genetics/*metabolism; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; *Neovascularization, Physiologic; Nerve Tissue Proteins/genetics/*metabolism; Protein Transport; RNA Interference; Receptors, Vascular Endothelial Growth Factor/*metabolism; Retinal Neovascularization/genetics/*metabolism/physiopathology; Signal Transduction; Transfection; VEGF signaling; Vegfr2; angiogenesis; endothelial cell; endothelial cell sprouting and proliferation
External Publication Status:published
Document Type:Article
Communicated by:Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:From the Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Munster, Faculty of Medicine, Munster, Germany (M.v.L., M.N., K. Kato, J.M.K., R.H.A.); and Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (K. Kato, K. Kaibuchi). ralf.adams@mpi-muenster.mpg.de.
Identifiers:ISSN:1524-4636 (Electronic) 1079-5642 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/26069237 [ID No:2]
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