A Mechanism for Modulation of Cellular Responses to VEGF Activation of the Integrins

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-κB activation and endothelial cell survival

“…PKB/Akt requires intact actin cytoskeleton to prevent TNF-induced death LY294002 pretreatment decreased integrin-mediated HUVEC adhesion, while constitutive active PKB/Akt enhanced it (Figure 5a), consistent with the reported integrin affinity modulation by PKB/Akt (Byzova et al, 2000). As ligated integrins promote actin stress fiber formation (Alghisi and Ruegg, 2006), we tested whether actin polymerization was necessary for HUVEC survival.…”

The integrin coactivator Kindlin-2 plays a critical role in angiogenesis in mice and zebrafish

“…These observations are in accord with our previous studies demonstrating that VEGF is a potent stimulator of the ␣V␤3 activation and ␣V␤3-dependent EC functions via VEGFR2-dependent inside-out signaling. 6,7 Thus, the kindlin-2 ϩ/Ϫ phenotype demonstrates a critical role of ␤3 integrins in angiogenesis in vivo in the absence of compensatory increases in VEGFR2. However, kindlin-2 also promotes the ␤3 integrin functions via other inside-out signaling pathways, for example, PKC-dependent For personal use only.…”

“…Particularly relevant to angiogenesis is the ability of VEGF to activate integrin ␣V␤3 and ␣5␤1 by engaging one of its EC receptors, VEGFR2. 6 Indeed, VEGFR2 and integrin ␣V␤3 can form a physical complex in EC and influence the functions of each other. 6,7 Two sets of cytoskeletal proteins, the talins and the kindlins, bind to the ␤ cytoplasmic tails and are now known to be involved in integrin activation.…”

“…6 Indeed, VEGFR2 and integrin ␣V␤3 can form a physical complex in EC and influence the functions of each other. 6,7 Two sets of cytoskeletal proteins, the talins and the kindlins, bind to the ␤ cytoplasmic tails and are now known to be involved in integrin activation. [8][9][10] Talin has long been known to be critical for integrin activation 11 and more recent studies have shown an obligatory requirement for the kindlins in integrin activation in the context of intact cells and whole organisms.…”

Normalization of the Ovarian Cancer Microenvironment by SPARC

“…VEGF is known to exert an autocrine as well as paracrine mitogenic effect on a variety of tumor cells including melanoma, prostate cancer, and ovarian cancer in vivo (22,(35)(36)(37)(38). Our pilot studies indicated that VEGF stimulates the proliferation of ID8 cells in a concentration-dependent manner (data not shown).…”