Cooperation between integrin ανβ3 and VEGFR2 in angiogenesis

Abstract

The cross-talk between receptor tyrosine kinases and integrin receptors are known to be crucial for a number of cellular functions. On endothelial cells, an interaction between integrin α v β 3 and VEGFR2 seems to be particularly important process during vascularization. Importantly, the functional association between VEGFR2 and integrin α v β 3 is of reciprocal nature since each receptor is able to promote activation of its counterpart. This mutually beneficial relationship regulates a number of cellular activities involved in angiogenesis, including endothelial cell migration, survival and tube formation, and hematopoietic cell functions within vasculature. This article discusses several possible mechanisms reported by different labs which mediate formation of the complex between VEGFR-2 and α v β 3 on endothelial cells. The pathological consequences and regulatory events involved in this receptor cross-talk are also presented.

Interplay between αvβ3 Integrin and Nucleolin Regulates Human Endothelial and Glioma Cell Migration

“…In the present study it is shown that PTN also increases cell surface NCL localization, and that expression of ␣ v ␤ 3 and ␤ 3 Tyr 773 phosphorylation are required for the redistribution of NCL from the nucleus to the cell membrane. VEGF has been shown to induce expression (34) and c-Src-mediated phosphorylation of ␤ 3 at Tyr 773 (35), which based on our data, provide an explanation for the VEGF-stimulated NCL cell surface localization. Laminin-1-induced increase of NCL cell surface localization relies on an integrin-dependent cascade (33), supporting our notion that integrins regulate NCL cell surface localization.…”

“…In the same line are also data showing that many of the molecules that have been described to bind and act through cell surface NCL are also described to act through integrins, and especially ␣ v ␤ 3 . This is true for VEGF (34,35), laminins (15,36,37), hepatocyte growth factor (13,38), endostatin (14,39), and PTN (18,24).…”

Thrombospondin-1 Inhibits VEGF Receptor-2 Signaling by Disrupting Its Association with CD47

“…Future studies will also focus on whether CD47 associates differentially with these processed forms of VEGFR2. Finally, the effects of CD47 ligation on the known associations of VEGFR2 with VE-cadherin, integrins, IQGAP1, and CD36 should be further examined (53)(54)(55).…”

VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice

“…developing brain (Bozoyan et al 2012) and retina (Gerhardt et al 2003, Scott et al 2010. Proliferation of endothelial cells is mainly regulated by the signaling of VEGFA and VEGFR2 in the developing vasculature (Gerhardt et al 2003, Somanath et al 2009). The expression level of total Vegfa mRNA is high during early embryonic period but it gradually decreases along with brain maturation (Ng et al 2001, Mackenzie & Ruhrberg 2012.…”

“…Therefore, continuous angiogenesis is almost absent in adult mammalian brains except under pathological conditions such as injury or hypoxia (Brown & Thore 2011). In the angiogenic vasculature, proliferation of endothelial stalk cells and filopodia extension of endothelial tip cells are principally regulated by the signaling of VEGFA and VEGF receptor 2 (VEGFR2 (KDR); Gerhardt et al 2003, Somanath et al 2009). The deficiency of Vegfa or Vegfr2 genes appears to be lethal due to abnormal blood vessel development (Shalaby et al 1995, Carmeliet et al 1996.…”