Neuropilin-2 (NRP-2) which is related to NRP-1, is a type I? transmembrane glycoprotein and has the structure characteristic with five main extracellular domains: two complement binding (CUB) domains, two coagulation factor V/VIII homology domains, and a MAM (meprin, tyrosine phosphatase domain) region. NRP-2 is a receptor capable of binding two disparate ligands, classⅢ semaphorins (SEMA) and vascular endothelial growth factors (VEGF), and thus regulates two diverse systems by activating cellular signaling pathways via interacting with other cell surface receptors such as VEGF receptors and plexins. NRP-2 is well known for its role in facilitating axonal guidance during the development of the neuronal system, and additionally, it is also expressed in vascular endothelial cells and lymphatic endothelium where it affects proliferation, migration, angiogenesis, as well as the formation of small lymphatic vessels and capillaries. A recent study has identified NRP-2 as a polysialylation protein expressed in human dendritic cells and modulates DC-T Cell Interactions. Nearly all tumor cells express neuropilins and NRP-2 is predominantly expressed in neuronal tumors and melanomas. Furthermore, it is suggested that as the specific ligand for NRP-2, SEMA 3F inhibits tumor angiogenesis, and metastasis.
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