Platelet-derived Growth Factor Receptor β and Vascular Endothelial Growth Factor Receptor 2 Bind to the β3Integrin through Its Extracellular Domain*

By E. Borges, Y. Jan, Erkki Ruoslahti. Journal of Biological Chemistry, 2000

283 citations recorded by the source corpus.

Integrin-mediated cell attachment and growth factor stimulation often act synergistically on cell proliferation, differentiation, migration, and survival. Some of these synergistic effects depend on the physical interaction of integrins with growth factor receptors. Here we examine the nature of the physical interaction between the αvβ3 integrin and two receptor tyrosine kinases (RTKs), the platelet-derived growth factor receptor β (PDGF-Rβ) and the vascular endothelial growth factor receptor 2 (VEGF-R2, also known as KDR and flk-1). Both of these RTKs associate with the αvβ3 integrin but do not associate with β1 integrins. Furthermore, growth factor stimulation of these RTKs promotes increased cell proliferation and migration when cells are attached to the αvβ3 ligand, vitronectin. We show that αvβ3 in which the β3cytoplasmic domain is deleted or replaced with the β1cytoplasmic domain coimmunoprecipitates with PDGF-Rβ and VEGF-R2. The β3 extracellular domain alone was sufficient for the PDGF-Rβ association whereas the VEGF-R2 association required the presence of the αv subunit. Activation of the RTKs by their ligands was not required for them to associate with the integrin. Cell migration to PDGF was enhanced in the cells transfected with the chimeric subunit containing the β3 extracellular domain but not when that domain came from the β1 subunit. These results show that the interactions that lead to the association of the αvβ3 integrin with PDGF-Rβ and VEGF-R2 and enhancement of RTK activity take place outside the cell.

Subfields: Cancer Research, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/42f6fdf73aa0443b9ba36391c9fdbdd72eed72a2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. L. Claesson‐Welsh
2. Erkki Ruoslahti
3. D. Cheresh

In Immunology and Allergy

1. D. Cheresh
2. L. Claesson‐Welsh
3. S. Koch
4. Rakesh K. Jain

In Molecular Biology

1. D. Cheresh
2. L. Claesson‐Welsh
3. Erkki Ruoslahti
4. S. Koch
5. Rakesh K. Jain

Citations in the corpus

• Specialization of tumour vasculature (2002, background): “Finally, the αvβ3 integrin physically associates with VEGFR2, and the binding of αvβ3 to its ECM ligands increases VEGF signalling in cell culture”
• α4β1- and α6β1-integrins are functional receptors for midkine, a heparin-binding growth factor (2004, methodology): “We analysed this point using an approach similar to that of Borges et al. (Borges et al., 2000), namely transfection and coprecipitation.”
• Signal transduction by vascular endothelial growth factor receptors. (2012, background): “The b3 subunit binds VEGFR2 through its extracellular domain and the complex is stabilized by the av subunit (Borges et al. 2000; Liu et al. 2009).”
• Get a ligand, get a life: integrins, signaling and cell survival (2002, background): “The integrin requirement for growth factor signaling is partly explained by the physical association of several growth factor receptors with integrins (Borges et al., 2000; Falcioni et al., 1997; Lee and Juliano, 2000; Miyamoto et al., 1996; Eliceiri, 2001).”