IndraLab

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"It is notable that VEGF-A binds to both NRP-1 and NRP-2, but has higher affinity for NRP-1 due to amino acid substitutions within the first loop region of NRP-1 that provide additional contacts between NRP-1 Thr299 and VEGF-A Glu154 (Figure 1B, C) ."

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"VEGFA and VEGFC can interact with NRP1 and NRP2 and, as described above, VEGFA and NRP1 and VEGFC and NRP2 stimulate autocrine loops in ccRCC cells."

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"NRPa-308 inhibited VEGFA and NRP1 and VEGFA and NRP2 binding in a dose dependent manner but surprisingly, inhibited VEGFC and NRP2 binding in a reverse dose dependent manner."

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"NRP1 and NRP2, originally discovered as neuronal receptors for semaphorins, bind the most common splice-variant of VEGF-A (VEGF ) and form a complex with VEGFR-2 and VEGFR-1 to regulate their signalling (Fuh et al., 2000)."

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"VEGF-A 165 binds to NRP1 and NRP2, whereas VEGF-A 145 binds only to NRP2 [XREF_BIBR, XREF_BIBR]."

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"Among other ligand-receptor pairs, MAPK/ERK pathway is activated by VEGFA binding to its receptor NRP2 which leads to a phosphorylation and nuclear localisation of GLI1."

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"VEGF-A binds to NRP1 and NRP2 but the affinity depends on the splice variants of VEGF-A."

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"Similarly, NRP-2 also binds VEGF-A 165 with high affinity [XREF_BIBR]."

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"Neuropilin-2 binds VEGF-A, VEGF-C, VEGF-D and PlGF, then complexes with VEGFR-1, VEGFR-2 or VEGFR-3."

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"The VEGF-A 145 isoform, which lacks exon 7, binds NRP2, presumably through its exon-6-encoded domain [XREF_BIBR]."

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"Given that weak binding of VEGF-A 165 appears to occur at concentrations of VEGF-A 165 required for biological effects in endothelial cells such as migration or angiogenesis, such as were used in this study, the biological relevance of VEGF-A 165 binding to NRP2 in cells is unclear."

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"The MT-group displayed interactions involving crucial pairs such as CLU-TREM2, LGALS3-MERTK, PGF-NRP2, and VEGFA-NRP2."

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"Considering that the interaction of S1 CendR peptide with NRP-1 mimics that of its endogenous partner VEGF-A 164, the possible basis of differential binding of VEGF-A to NRP-1 and NRP-2 could be relevant to that of S1 to the two NRP isoforms."

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"To our surprise, in our study, we found that NRP-2 (an isoform of NRP-1)-related ligand-receptor interactions, specifically the NRP-2-SEMA3C and NRP-2-VEGFA interactions between CAFs/endothelial cells/DCs/macrophages/tumor cells and other cells, were relatively stronger in responders than in nonresponders."

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"The closely related neuropilin-2 (Np-2) also binds VEGF-A 165 (but not VEGF-A 121), as well as VEGF-A 145 and PlGF-2, strongly implying that both Np-1 and Np-2 in angiogenesis [XREF_BIBR - XREF_BIBR]."

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"Cell-cell communication analysis identified several important receptor-ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa)."

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"Accordingly, the disruption of NRP1 or NRP2 binding to VEGF-A (165) or HGF with a blocking antibody, decreased the proliferation and migration of endothelial cells."

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"Neuropilin-2 is also able to bind VEGF-A 165, but unlike neuropilin-1, it also interacts with VEGF-A 145 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

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"VEGF-A also binds NRP2 similarly ( xref , xref ), and, therefore, the structure results demonstrate that aNRP2-10 occupies the binding site of VEGF-A or VEGF-C and blocks their access to the NRP2 binding pocket."

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"It showed that the VEGFA-NRP1 and VEGFA-NRP2 ligand-receptor pairs were enriched in both the primary and liver metastatic tumors."

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"The KKK/QNG L3-loop produces the largest net gain in Nrp2 binding to VEGF-A. Conserved residues in the L3 loop form one wall of the C-terminal arginine binding pocket."

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"VEGF-A also binds NRP2 similarly (25, 26), and, therefore, the structure results demonstrate that aNRP2-10 occupies the binding site of VEGF-A or VEGF-C and blocks their access to the NRP2 binding pocket."

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"VEGF-A 165 but not VEGF-A 121 interacts with neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2), which are cell surface transmembrane glycoprotein receptors [XREF_BIBR]."

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"Within the VEGF family, NRP1 binds VEGF-A, -B, -E and placenta growth factor (PlGF2), whereas NRP2 binds VEGF-A, -C, -D, and PlGF2."

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"NRP2 specifically binds VEGF-A and VEGF-C, although the biological relevance of these interactions in human endothelial cells is poorly understood."

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"Furthermore, NRP2 is co-expressed with NRP1 in endothelial and other cell types, NRP2 and NRP1 may associate to form heterodimers 14, and NRP2 also binds to VEGF-A in trimeric complexes with VEGF receptor 2 21, 22, suggesting that NRPs have the potential to interact in a cooperative fashion in the endothelium."

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"Among the top signaling interactions, we found expression of VEGF ligand-receptor pairs in the liver and heart (FLT4:VEGFC; VEGFA: KDR; NRP2:VEGFA; VEGFA:FLT1)."

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"NRP1 interacts with heparin-binding isoforms of VEGF-A, -B, -E and PGF, whereas NRP2 interacts with VEGF-A, -C and -D [40–42] ."

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"A chimeric Nrp2, which combines the identified mutations, is capable of binding VEGF-A similarly to Nrp1 whereas a chimeric Nrp1 shows significant loss of VEGF-A binding."

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"Neuropilin-2 is also able to bind VEGF-A 165 , but unlike neuropilin-1, it also interacts with VEGF-A 145 [ xref , xref , xref ]."

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"Within the VEGF family, NRP1 binds VEGF-A, -B, -E and placenta growth factor (PlGF2), whereas NRP2 binds VEGF-A, -C, -D, and PlGF2 ( xref ; xref )."

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"VEGF-A also interacts with coreceptors heparin sulfate proteoglycans, neuropilin-1, and neuropilin-2, which are also located on the surface of endothelial cells."

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"Similarly, NRP-2 also binds VEGF-A 165 with high affinity [ xref ]."

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"TML macrophages were predicted to interact with Schwann cells, contributing to synapse formation and axon guidance ( VEGFA–NRP1 ,  VEGFANRP2 , SEMA3C– NRP2 and SEMA3E – PLXND1 ) xref (Extended Data Fig. xref and Supplementary Table xref )."

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"The closely related neuropilin-2 (Np-2) also binds VEGF-A 165 (but not VEGF-A 121 ), as well as VEGF-A 145 and PlGF-2, strongly implying that both Np-1 and Np-2 in angiogenesis [ xref - xref ]."

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"This finding aligns with previous studies showing significantly higher levels of PGR in glandular epithelium in EPs. xref Furthermore, angiogenesis signaling, particularly the VEGFANRP2 interaction, demonstrated increased activity between mast cells and endothelial cells (Figure  xref )."

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"Given that weak binding of VEGF-A 165 appears to occur at concentrations of VEGF-A 165 required for biological effects in endothelial cells such as migration or angiogenesis, such as were used in this study, the biological relevance of VEGF-A 165 binding to NRP2 in cells is unclear."

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"The KKK and QNG L3-loop produces the largest net gain in Nrp2 binding to VEGF-A."

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"Thus it is plausible that the major mechanism through which NRP2 contributes to VEGF-A 165 –dependent migration in human endothelial cells is through heterodimerization with NRP1 rather than direct binding of VEGF-A 165 to NRP2."

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"We also noted ligand–receptor interactions recently described between epicardial cells and CMs (NRP2VEGFA), endothelial cells (MIF–TNFRSF10D) and fibroblasts (NRP2–SEMA3C) in human embryos xref (Fig. xref and Extended Data Fig. xref )."

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"VEGF-A 165 binding to NRP1 and NRP2 is important for migration of endothelial cells."

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"NRP2 also binds VEGF-A isoforms and class 3 semaphorins, with preferential binding of VEGF145 and SEMA3F over VEGF165 and SEMA3A, respectively [XREF_BIBR]."

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"In addition to binding to the VEGF TK receptors, VEGF-A isoforms featuring exon 7 also bind to the single pass transmembrane receptors Neuropilin 1 (NRP1) and NRP2."

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"It is notable that VEGF-A binds to both NRP-1 and NRP-2, but has higher affinity for NRP-1 due to amino acid substitutions within the first loop region of NRP-1 that provide additional contacts between NRP-1 Thr299 and VEGF-A Glu154 14."
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"The NRP-2 binds specifically to VEGF-A and VEGF-C."

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"In addition, because many endothelial cells, including HUVECs, coexpress NRP1 and NRP2, and both are known to bind VEGF-A 165 , we also examined whether non-VEGF-binding NRP1 mutants affected VEGF-A 165 binding to NRP2."

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"Initial studies showed that VEGF-A binding to VEGFR-2/NRP1 or NRP2 receptor complexes promoted endothelial cell proliferation, migration, and tube formation in vitro as well as angiogenesis in vivo. xref , xref , xref , xref In endothelial cells, NRPs enhance the binding of VEGF-A 165 to its receptor and increase ERK1/2 MAPK activation. xref The VEGF-A/NRP1/proline-rich TK2 (PYK2/PTK2B)/p130Cas (BCAR1) axis is also required for endothelial cell chemotaxis. xref NRP2 promotes lymphangiogenesis through a mechanism involving VEGF-C and VEGFR-3. xref Blocking the VEGF-C binding site with an NRP2-blocking antibody inhibits tumor lymphangiogenesis and metastatic spread to local lymph nodes and distant sites. xref In addition to its effects on angiogenesis, VEGF-A 165 promotes tumor cell survival through an NRP- and PI3K/AKT-dependent mechanism. xref – xref VEGF-A 165 also promotes physical interaction between NRP1 and c-MET, facilitates c-MET, Src kinase, and STAT3 activation, and leads to the upregulation of the pro-survival factor, MLC-1. xref VEGF-C binding to NRP2 prevents oxidative stress and promotes cancer cell survival and autophagy. xref , xref While the mechanism is unknown, the VEGF-C/NRP2 axis inhibits mammalian target of rapamycin complex (mTORC)-1 activity, relieving its suppression of autophagy and thus contributing to tumor cell survival under stress."

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"Members of the VEGF family bind to the VEGFRs or co-receptors with different affinities : VEGF-A primarily binds to VEGFR-1, VEGFR-2, NRP-1 and NRP-2, while VEGF-B binds to VEGFR-1 and NRP-1."

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"In addition to Sema3, Nrp1 and Nrp2 also bind to vascular endothelial growth factor-A (VEGF-A) and -C (VEGF-C) family members respectively and function as their co-receptors."

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"In addition, VEGFA-NRP1 and VEGFA-NRP2 interacting in HCC participate in signaling pathways controlling cell migration [ xref ]."

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"Hence, though VEGF-A interacts with both NRP-1 and NRP-2, it exhibits a fifty-fold greater affinity for NRP-1."

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"It is notable that VEGF-A binds to both NRP-1 and NRP-2 but has higher affinity for NRP-1 due to amino acid substitutions within the first loop region of NRP-1 that provide additional contacts between NRP-1 Thr299 and VEGF-A Glu154 (Figure 1B,C)."