Signal transduction by vascular endothelial growth factor receptors

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Biochemical Journal (Impact Factor: 4.4). 07/2011; 437(2):169-83. DOI: 10.1042/BJ20110301
Source: PubMed


VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling.

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    • "VEGF also binds to non-tyrosine-kinase receptors of the neuropilinfamily , NRP1 and NRP2, which act as co-receptors of the other VEGFR [1]. After VEGF binding, tyrosine-kinase receptors dimerize, followed by conformational changes that finally lead to the activation of a downstream signaling cascade [1]. For example, phosphorylation of the tyrosineresidue 1214 in the VEGFR-2 is known to activate signaling cascades for actin reorganization in endothelial cells [2]. "
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    • "Angiogenesis is important in tumor growth and metastasis . It is primarily driven by VEGF-A (Vascular Endothelial Growth Factor) [124], acting through binding on VEGF Re- ceptor-2 (VEGFR-2) [125], the latter expressed on endothelial cells. VEGFR-2 engagement by VEGF results in endothelial cell proliferation, migration and motility [126], while VEGFR-1 is thought to act as a decoy receptor. "
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