ArticleCell stress & chaperones2003
Integrin alphavbeta3, requirement for VEGFR2-mediated activation of SAPK2/p38 and for Hsp90-dependent phosphorylation of focal adhesion kinase in endothelial cells activated by VEGF.
Article in Cell stress & chaperones, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 121 citations in OpenAlex.
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- Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma.Acta neuropathologica communications · 2022Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Human SMILE-Derived Stromal Lenticule Scaffold for Regenerative Therapy: Review and Perspectives.International journal of molecular sciences · 2022Review
- Pulling back the curtain: The hidden functions of receptor tyrosine kinases in development.Current topics in developmental biology · 2022Article
- Prolyl 3-Hydroxylase 2 Is a Molecular Player of Angiogenesis.International journal of molecular sciences · 2021Article
- Engineering a Chemically Defined Hydrogel Bioink for Direct Bioprinting of Microvasculature.Biomacromolecules · 2021Article
- Coatings in Decellularized Vascular Scaffolds for the Establishment of a Functional Endothelium: A Scoping Review of Vascular Graft Refinement.Frontiers in cardiovascular medicine · 2021Article
- Review of Integrin-Targeting Biomaterials in Tissue Engineering.Advanced healthcare materials · 2020Review
- The role of microenvironment in tumor angiogenesis.Journal of experimental & clinical cancer research : CR · 2020Review
- Cancer-associated fibroblasts regulate endothelial adhesion protein LPP to promote ovarian cancer chemoresistance.The Journal of clinical investigation · 2018Article
- The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells.Oncotarget · 2017Review
- Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma.Molecular cancer · 2017Article
- A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis.Nature communications · 2017Article
- The novel VEGF receptor 2 inhibitor YLL545 inhibits angiogenesis and growth in breast cancer.Oncotarget · 2016Article
- Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.Journal of biomedical materials research. Part A · 2016Article
- Tuning cell migration: contractility as an integrator of intracellular signals from multiple cues.F1000Research · 2016Review
- Anti-metastatic action of FAK inhibitor OXA-11 in combination with VEGFR-2 signaling blockade in pancreatic neuroendocrine tumors.Clinical & experimental metastasis · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cell migration, a key process in angiogenesis, requires the coordinated integration of motogenic signals elicited by the adhesion of endothelial cells to extracellular matrices and by angiogenic cytokines such as the vascular endothelial growth factor (VEGF). In this study, we found that addition of VEGF to human umbilical vein endothelial cells cultivated on vitronectin triggers a synergistic interaction between the VEGF receptor VEGFR2 and the clustered integrin receptor alphavbeta3. The interaction between VEGFR2 and alphavbeta3 is required for full phosphorylation of VEGFR2 and to drive the activation of motogenic pathways involving focal adhesion kinase (FAK) and stress-activated protein kinase-2/p38 (SAPK2/p38). The signal emanating from the VEGFR2 and alphavbeta3 interaction and leading to SAPK2/p38 activation proceeds directly from VEGFR2. The chaperone Hsp90 is found in a complex that coprecipitates with inactivated VEGFR2, and the association is increased by VEGF and decreased by geldanamycin, a specific inhibitor of Hsp90-mediated events. Geldanamycin also impairs the phosphorylation of FAK that results from the interaction between VEGFR2 and alphavbeta3, and this is accompanied by an inhibition of the recruitment of vinculin to VEGFR2. We conclude that a necessary cross talk should occur between VEGFR2 and the integrin alphavbeta3, to transduce the VEGF signals to SAPK2/p38 and FAK and that Hsp90 is instrumental in the building up of focal adhesions by allowing the phosphorylation of FAK and the recruitment of vinculin to VEGFR2.
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