IndraLab

Statements


1 | 28 11

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

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

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

reach
"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."

No evidence text available

reach
"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."

reach
"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."

sparser
"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."

reach
"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."

reach
"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)."

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

reach
"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]."

reach
"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."

reach
"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) ."

reach
"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."

reach
"15 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)."

sparser
"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."

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

reach
"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)."

sparser
"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 ]."

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

reach
"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."

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

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

sparser
"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."

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

sparser
"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."

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

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

reach
"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."

reach
"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."

sparser
"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."

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

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

sparser
"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 )."

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

reach
"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]."

sparser
"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."

reach
"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]."

reach
"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."