Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1)
Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) is a tyrosine kinase and receptor for VEGF, VEGF-B, and PlGF. It plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. It plays an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. VEGFR-1 can promote endothelial cell proliferation, survival, and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. It promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts. VEGFR-1 has very high affinity for VEGF-A and relatively low protein kinase activity. Likewise, isoforms lacking a transmembrane domain such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGF-A. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG-1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. It mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Isoform 1 phosphorylates PLCG1. Isoform 7 mediates phosphorylation of SRC at 'Tyr-418' and promotes tumor cell invasion. The soluble or truncated form of VEGFR-1 has inhibitory effects opposite to that of “full length”-membrane bound form. The soluble form can be found in sera, plasma, and at high concentration in placenta. Elevated levels of sVEGFR-1 have been reported in preeclampsia.
Swiss-Prot Accession Number: P17948