VEGF-activated neuropilin signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by vascular endothelial growth factor (VEGF) binding to a neuropilin protein on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:rl, PMID:12852851]

VEGF, a potent angiogenic and permeability factor, activates the neuropilin signaling pathway through its binding to neuropilin-1 (NRP1) and neuropilin-2 (NRP2). NRP1 and NRP2 are transmembrane receptors that act as coreceptors for VEGF and other ligands, including Semaphorins. Upon VEGF binding, NRP1 and NRP2 form complexes with VEGF receptor 2 (VEGFR2), a tyrosine kinase receptor, enhancing VEGF signaling. The NRP1/VEGFR2 and NRP2/VEGFR2 complexes trigger downstream signaling cascades that ultimately lead to angiogenesis, vascular permeability, and cell survival. The interaction between NRP and VEGFR2 is facilitated by the interaction between the b1 domain of NRP and the α3 domain of VEGFR2. This interaction is crucial for the activation of VEGFR2 and the subsequent initiation of downstream signaling. The activation of VEGFR2 leads to the phosphorylation of tyrosine residues within its intracellular domain, creating docking sites for various signaling molecules, such as phospholipase C-gamma (PLC-gamma) and phosphoinositide 3-kinase (PI3K). PLC-gamma activates the calcium signaling pathway, while PI3K activates the AKT pathway. These pathways promote cell survival, proliferation, and migration, contributing to the angiogenic process. Additionally, VEGF binding to NRP1 and NRP2 can activate the Ras/MAPK pathway, which further enhances cell growth and survival. In summary, VEGF-activated neuropilin signaling pathway involves the formation of NRP/VEGFR2 complexes, the activation of downstream signaling cascades such as PLC-gamma, PI3K, and Ras/MAPK, and the subsequent induction of angiogenesis, vascular permeability, and cell survival.'
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Proteins (2)

Compounds (7)