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VEGFR-2Vascular Endothelial Growth Factor Receptor-2
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AMC303 is a cyclic peptide targeting CD44v6, a key cell membrane protein in pathways of several receptor-tyrosine kinases, such as c-MET, VEGFR-2 and RON.
VEGFR-2, another vascular growth factor receptor, is expressed in the epithelium as a soluble protein, namely, sVEGFR-2 [99].
PGF not only activates its own signaling via VEGFR-1 that is independent of VEGFA, but also enhances VEGF signaling by displacing VEGFA from VEGFR-1 to VEGFR-2, which subsequently amplifies VEGFR-2 signaling (10).
VEGFR-2 dimerization activates the intracellular serine/threonine kinase Raf, the dual specificity MAPK kinase (MEK), and the MAPK-ERK pathway upon stimulation, leading to increased DNA synthesis and cell proliferation.
This factor plays important pleotropic effects on endothelial cells, by interacting with VEGFR-2 and transient receptor potential canonical-1 (TRPC-1) cation channel to control cellular homeostasis [64].
More than 95% of the cultured cells were positively stained both with Dil-AcLDL and FITC-UE-lectin under a fluorescence microscope and showed CD31 and VEGFR-2 expression on cell surface, as it was confirmed by FACS.
A VEGF-A splice variant defective for heparan sulfate and neuro-pilin-1 binding shows attenuated signaling through VEGFR-2. Cell Mol Life Sci 2006:63(17):20672077.
There are several evidences that VEGFR-1, existing either as a membrane bound form or as a soluble form [33], may act as a VEGF trap due to its poor kinase activity and high-affinity to VEGF, moderating the amount of free VEGF available to activate VEGFR-2 [34], the key receptor mediating most of cellular effects of VEGF in the endothelium [1, 2].
Several VEGF receptors have been identified on the surface of epidermal keratinocytes including VEGFR-1, VEGFR-2, and NRP-1 [95].
VEGFs play their role in angiogenesis through binding to three different receptors located on cell membrane: VEGFR-1 (Flt-1), VEGFR-2 (Flk/KDR), and VEGFR-3 (Flt4) (Figure 1).
Cediranib is an inhibitor of VEGFR-1, VEGFR-2, and VEGFR-3; c-kit; FGFR-1; and PDGFR-[alpha] and Platelet-derived growth factor receptor alpha (PDGFR-[alpha]) and PDGFR-[beta]eta.
There are 7 types of VEGF family and VEGF-A with two receptors VEGFR-1 and VEGFR-2 that are most important in angiogenesis [6, 7].