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http://purl.uniprot.org/citations/20431062http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20431062http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20431062http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Integrins cooperate with growth factor receptors to promote downstream signaling for cell proliferation and migration. However, the mechanism of receptor activation is still unknown.

Objective

To analyze the mechanism of phosphorylation of the vascular endothelial growth factor receptor (VEGFR)-3 by cell adhesion.

Methods and results

We show that VEGFR-3 phosphorylation, induced by cell attachment to the extracellular matrix, is independent from the intrinsic kinase activity of the receptor, as evidenced from phosphorylation cell adhesion experiments with a mutant kinase dead receptor or in the presence of the specific kinase inhibitor MAZ 51. Cell adhesion experiments in the presence of the c-Src inhibitor PP2 or in fibroblast triple knockout for c-Src, Yes, and Fyn (SYF) demonstrate that VEGFR-3 phosphorylation, induced by extracellular matrix, is mediated by c-Src. Kinase assays in vitro with recombinant c-Src show that VEGFR-3 is a direct c-Src target and mass spectrometry analysis identified the sites phosphorylated by c-Src as tyrosine 830, 833, 853, 1063, 1333, and 1337, demonstrating that integrin-mediated receptor phosphorylation induces a phosphorylation pattern that is distinct from that induced by growth factors. Furthermore, pull-down assays show that integrin-mediated VEGFR-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins CRKI/II and SHC inducing activation of JNK.

Conclusions

These data suggest that cell adhesion to extracellular matrix induces a downstream signaling using the tyrosine kinase receptor VEGFR-3 as scaffold."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.109.206326"xsd:string
http://purl.uniprot.org/citations/20431062http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.109.206326"xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Terstappen G.C."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Terstappen G.C."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Galvagni F."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Galvagni F."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Oliviero S."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Oliviero S."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Salameh A."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Salameh A."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Orlandini M."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Orlandini M."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Neri F."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Neri F."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Gotta S."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Gotta S."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Matteucci G."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Matteucci G."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Pennacchini S."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Pennacchini S."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Petraglia F."xsd:string
http://purl.uniprot.org/citations/20431062http://purl.uniprot.org/core/author"Petraglia F."xsd:string
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