Platelet-derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain.
Platelet-derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain.
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发表时间：
2000
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通讯作者：
E. Borges;Y. Jan;E. Ruoslahti
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作者：
E. Borges;Y. Jan;E. Ruoslahti
整合素介导的细胞附着和生长因子刺激通常协同作用于细胞增殖、分化、迁移和存活。其中一些协同作用依赖于整合素与生长因子受体的物理相互作用。在这里，我们研究了α (v) β(3)整合素与两种受体酪氨酸激酶（rtk）、血小板衍生生长因子受体β (PDGF-Rbeta)和血管内皮生长因子受体2 （VEGF-R2，也称为KDR和flk-1）之间的物理相互作用的性质。这两种rtk都与α (v) β(3)整合素相关，但不与β(1)整合素相关。此外，当细胞与α (v) β(3)配体（玻璃体连接蛋白）结合时，生长因子刺激这些RTKs可促进细胞增殖和迁移。我们发现β(3)胞质结构域被删除或被β(1)胞质结构域取代的α (v) β(3)与PDGF-Rbeta和VEGF-R2共免疫沉淀。单独的β(3)胞外结构域对于PDGF-Rbeta关联是足够的，而VEGF-R2关联需要α (v)亚基的存在。rtk与整合素结合并不需要它们的配体激活。在转染含有β(3)胞外结构域的嵌合亚基的细胞中，细胞向PDGF的迁移增强，但当该结构域来自β(1)亚基时，细胞向PDGF的迁移没有增强。这些结果表明，导致α (v) β(3)整合素与PDGF-Rbeta和VEGF-R2结合以及RTK活性增强的相互作用发生在细胞外。
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 alpha(v)beta(3) integrin and two receptor tyrosine kinases (RTKs), the platelet-derived growth factor receptor beta (PDGF-Rbeta) and the vascular endothelial growth factor receptor 2 (VEGF-R2, also known as KDR and flk-1). Both of these RTKs associate with the alpha(v)beta(3) integrin but do not associate with beta(1) integrins. Furthermore, growth factor stimulation of these RTKs promotes increased cell proliferation and migration when cells are attached to the alpha(v)beta(3) ligand, vitronectin. We show that alpha(v)beta(3) in which the beta(3) cytoplasmic domain is deleted or replaced with the beta(1) cytoplasmic domain coimmunoprecipitates with PDGF-Rbeta and VEGF-R2. The beta(3) extracellular domain alone was sufficient for the PDGF-Rbeta association whereas the VEGF-R2 association required the presence of the alpha(v) 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 beta(3) extracellular domain but not when that domain came from the beta(1) subunit. These results show that the interactions that lead to the association of the alpha(v)beta(3) integrin with PDGF-Rbeta and VEGF-R2 and enhancement of RTK activity take place outside the cell.