File:Endothelial cell signaling cartoon.jpeg
Figure 1. Cross-talk between growth factors and integrins in endothelial cells.
VEGF binding to VEGFR-2 results in receptor dimerization and phosphorylation of specific tyrosine residues within the intracellular domain of the receptor. PLC, Sck, and VRAP (not depicted) all interact directly with VEGFR-2. The mechanism of activation of FAK, Src, MAPK, PI 3-kinase, and AKT by VEGFR-2 is less clearly understood. Recent work indicates that VEGF-mediated Src activation promotes FAK association with Vß5. The extracellular domain of ß3 directs association of Vß3 with VEGFR-2. Engagement of either VEGFR-2 or Vß3 enhances the function of the reciprocal receptor. Binding of ECM proteins to Vß3 triggers phosphorylation of tyrosine residues located in the intracellular domain of the ß3 chain and induces receptor clustering. Signaling molecules activated by ligation and/or clustering of Vß3 include FAK, Src, MAPK, PI 3-kinase, and Rho family members. Recent evidence suggests a role for an unidentified arachidonic acid (AA) metabolite in Vß3 activation of Rac. Phosphorylation of intracellular tyrosine residues of VEGFR-2 occurs in response to Vß3 ligation. The p53/bax pathway linked to apoptosis is suppressed by Vß3 engagement. The proapoptotic mediator caspase 8 may be activated by unligated Vß3-dependent membrane recruitment. Additionally, ligation of either Vß3 or Vß5 may influence the function of the reciprocal receptor.
Tiny dancers: the integrin-growth factor nexus in angiogenic signaling. Smyth SS, Patterson C. J Cell Biol. 2002 Jul 8;158(1):17-21. Epub 2002 Jul 8. Review. PMID: 12105178
- "VEGF-A, a factor that was initially identified based on its ability to increase vascular permeability and endothelial cell proliferation, is required for angiogenesis during development and is a necessary stimulus for hypoxia-induced angiogenesis. Four alternatively spliced isoforms of VEGF-A exist that bind two receptor tyrosine kinases, VEGF receptor (VEGFR)-1 (Flt-1) and VEGFR-2 (Flk-1/KDR), on the surface of endothelial cells. The FGF family is even more fecund, consisting of at least 20 members that act on four separate receptors. Binding of VEGFs and FGFs to their respective receptors triggers receptor tyrosine phosphorylation followed by recruitment of intracellular adaptor proteins and activation of signaling molecules"
Published 8 July 2002. doi:10.1083/jcb.200202100
© The Rockefeller University Press, 0021-9525/2002/7/17 $5.00 The Journal of Cell Biology, Volume 158, Number 1, July 8, 2002 17-21
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|current||17:33, 19 May 2009||1,280 × 979 (129 KB)||S8600021||Figure 1. Cross-talk between growth factors and integrins in endothelial cells. VEGF binding to VEGFR-2 results in receptor dimerization and phosphorylation of specific tyrosine residues within the intracellular domain of the receptor. PLC, Sck, and VRA|
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