The products of the neuropilin-1 (Np-1) and neuropilin-2 (Np-2) genes are receptors for factors belonging to the class 3 semaphorin family and participate in the guidance of growing axons to their targets. In the presence of heparin-like molecules, both receptors also function as receptors for the heparin-binding 165-amino acid isoform of vascular endothelial growth factor (VEGF165). Both receptors are unable to bind to the 121-amino acid isoform of vascular endothelial growth factor (VEGF121), which lacks a heparin-binding domain. Interestingly, complexes corresponding in size to125I-VEGF121·neuropilin complexes are formed when 125I-VEGF121 is bound and cross-linked to porcine aortic endothelial cells co-expressing VEGFR-1 and either Np-1 or Np-2. These complexes do not seem to represent complexes of 125I-VEGF121 with a truncated form of VEGFR-1, presumably formed as a result of the presence of Np-1 or Np-2 in the cells, because such truncated forms could not be detected with anti-VEGFR-1 antibodies. Antibodies directed against VEGFR-1 co-immunoprecipitated the125I-VEGF121·Np-2 sized cross-linked complex along with 125I-VEGF121·VEGFR-1 complexes from cells expressing both VEGFR-1 and Np-2 but not from control cells, indicating that VEGFR-1 and Np-2 associate with each other. To perform the reciprocal experiment we have expressed in porcine aortic endothelial cells a Np-2 receptor containing an in-framemyc epitope at the C terminus. Surprisingly, themyc-tagged Np-2 receptor lost most of its VEGF165 binding capacity but not its semaphorin-3F binding ability. Nevertheless, when Np-2myc was co-expressed in cells with VEGFR-1, it partially regained its VEGF165binding ability. Antibodies directed against the mycepitope co-immunoprecipitated125I-VEGF165·Np-2myc and125I- VEGF165·VEGFR-1 complexes from cells co-expressing VEGFR-1 and Np-2myc, indicating again that VEGFR-1 associates with Np-2. Our experiments therefore indicate that Np-2, and possibly also Np-1, associate with VEGFR-1 and that such complexes may be part of a cell membrane-associated signaling complex. The products of the neuropilin-1 (Np-1) and neuropilin-2 (Np-2) genes are receptors for factors belonging to the class 3 semaphorin family and participate in the guidance of growing axons to their targets. In the presence of heparin-like molecules, both receptors also function as receptors for the heparin-binding 165-amino acid isoform of vascular endothelial growth factor (VEGF165). Both receptors are unable to bind to the 121-amino acid isoform of vascular endothelial growth factor (VEGF121), which lacks a heparin-binding domain. Interestingly, complexes corresponding in size to125I-VEGF121·neuropilin complexes are formed when 125I-VEGF121 is bound and cross-linked to porcine aortic endothelial cells co-expressing VEGFR-1 and either Np-1 or Np-2. These complexes do not seem to represent complexes of 125I-VEGF121 with a truncated form of VEGFR-1, presumably formed as a result of the presence of Np-1 or Np-2 in the cells, because such truncated forms could not be detected with anti-VEGFR-1 antibodies. Antibodies directed against VEGFR-1 co-immunoprecipitated the125I-VEGF121·Np-2 sized cross-linked complex along with 125I-VEGF121·VEGFR-1 complexes from cells expressing both VEGFR-1 and Np-2 but not from control cells, indicating that VEGFR-1 and Np-2 associate with each other. To perform the reciprocal experiment we have expressed in porcine aortic endothelial cells a Np-2 receptor containing an in-framemyc epitope at the C terminus. Surprisingly, themyc-tagged Np-2 receptor lost most of its VEGF165 binding capacity but not its semaphorin-3F binding ability. Nevertheless, when Np-2myc was co-expressed in cells with VEGFR-1, it partially regained its VEGF165binding ability. Antibodies directed against the mycepitope co-immunoprecipitated125I-VEGF165·Np-2myc and125I- VEGF165·VEGFR-1 complexes from cells co-expressing VEGFR-1 and Np-2myc, indicating again that VEGFR-1 associates with Np-2. Our experiments therefore indicate that Np-2, and possibly also Np-1, associate with VEGFR-1 and that such complexes may be part of a cell membrane-associated signaling complex. vascular endothelial growth factor bis(sulfosuccinimidyl) suberate vascular endothelial growth factor receptor-1 vascular endothelial growth factor receptor-2 polyacrylamide gel electrophoresis 165-amino acid form of vascular endothelial growth factor 121-amino acid form of vascular endothelial growth factor neuropilin-1 neuropilin-2 porcine aortic endothelial cells semaphorin placenta growth factor phosphate-buffered saline alkaline phosphatase. The various forms of the growth factors belonging to the VEGF1 family (VEGF, PlGF, VEGF-B, VEGF-C, and VEGF-D) act as inducers and modulators of angiogenesis in vivo (1Neufeld G. Cohen T. Gengrinovitch S. Poltorak Z. FASEB J. 1999; 13: 9-22Crossref PubMed Scopus (3129) Google Scholar, 2Eriksson U. Alitalo K. Curr. Top. Microbiol. Immunol. 1999; 237: 41-57Crossref PubMed Scopus (151) Google Scholar, 3Persico M.G. Vincenti V. Dipalma T. Curr. Top. Microbiol. Immunol. 1999; 237: 31-40Crossref PubMed Scopus (145) Google Scholar). The active forms of the VEGF family members are synthesized as homodimers (4Leung D.W. Cachianes G. Kuang W.J. Goeddel D.V. Ferrara N. Science. 1989; 246: 1306-1309Crossref PubMed Scopus (4414) Google Scholar, 5Keck P.J. Hauser S.D. Krivi G. Sanzo K. Warren T. Feder J. Connolly D.T. Science. 1989; 246: 1309-1312Crossref PubMed Scopus (1794) Google Scholar) or as heterodimers with other VEGF family members such as PlGF (6DiSalvo J. Bayne M.L. Conn G. Kwok P.W. Trivedi P.G. Soderman D.D. Palisi T.M. Sullivan K.A. Thomas K.A. J. Biol. Chem. 1995; 270: 7717-7723Abstract Full Full PubMed Scopus Google Scholar). of the VEGF that angiogenesis is in containing a of the VEGF is therefore that the of of VEGF in vivo is for the of the N. K. PubMed Scopus Google Scholar, V. G. S. K. J. PubMed Scopus Google Scholar). forms of VEGF from to have (4Leung D.W. Cachianes G. Kuang W.J. Goeddel D.V. Ferrara N. Science. 1989; 246: 1306-1309Crossref PubMed Scopus (4414) Google Scholar, 5Keck P.J. Hauser S.D. Krivi G. Sanzo K. Warren T. Feder J. Connolly D.T. Science. 1989; 246: 1309-1312Crossref PubMed Scopus (1794) Google Scholar, Z. Cohen T. G. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, K.A. Ferrara N. J. Cachianes G. D.W. PubMed Scopus Google Scholar). These in the presence or the of the heparin-binding and to forms that in their and binding G. Cohen T. Poltorak Z. S. Gengrinovitch S. PubMed Scopus (145) Google Scholar). other VEGF family members such as PlGF and are also expressed in forms that in their binding ability. the of PlGF is in and a binding to not bind to V. G. M.G. Alitalo K. S. M.G. Google VEGF bind to the receptors VEGFR-1 S. T. Google Scholar) and Google Scholar). The binding of VEGF to (1Neufeld G. Cohen T. Gengrinovitch S. Poltorak Z. FASEB J. 1999; 13: 9-22Crossref PubMed Scopus (3129) Google Scholar, PubMed Scopus Google Scholar, K. Ferrara N. Science. PubMed Scopus Google Scholar, S. N. T. G. Google Scholar, S. Full PubMed Scopus Google Scholar) and is with the of endothelial cell and in vivo angiogenesis PubMed Scopus Google Scholar, J. J. Biol. Chem. Full PubMed Google Scholar). the of VEGFR-1 not seem to result in the of cell or have G. Vincenti V. G. M.G. Google Scholar, PubMed Scopus Google Scholar). the of VEGFR-1 to cell J. J. Biol. Chem. Full PubMed Google Scholar, N. G. S. 1995; Google Scholar, G. U. J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, S. PubMed Google Scholar). Both receptors in and the because of endothelial cells not and do not form J. M.L. 1995; PubMed Scopus Google Scholar). In of the the VEGFR-1 receptor not the of endothelial cells in but the of from endothelial cells was J. M.L. 1995; PubMed Scopus Google cells also of VEGF receptor a either or VEGFR-1 N. G. J. Biol. Chem. Full PubMed Google Scholar, S. G. J. Biol. Chem. Full PubMed Google Scholar). was that VEGF receptors of the endothelial cells are receptors that bind VEGF165 but not Cohen T. S. S. Gengrinovitch S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). experiments of and cell that of receptors S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The receptors from such cells VEGF165 and to be the products of the neuropilin-1 (Np-1) S. S. G. Full Full PubMed Scopus Google Scholar). was that the heparin-binding form of placenta growth factor and VEGF-B, members of the VEGF family of growth are also to bind to Np-1 S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, T. T. U. S. U. Alitalo K. J. Biol. Chem. 1999; Full Full PubMed Scopus Google Scholar). the of Np-1 as a VEGF receptor was it was that Np-1 in the as receptor for is a Np-1 that of growing of axons Z. Full Full PubMed Scopus Google Scholar, D.V. D.D. Full Full PubMed Scopus Google Scholar). was that is also to of endothelial cells S. J. Biol. 1999; PubMed Scopus Google Scholar). These indicate that signaling Np-1 angiogenesis and possibly the of the of the Np-1 in T. T. T. 1999; PubMed Google Scholar, T. T. T. Full Full PubMed Scopus Google Scholar, T. 1995; PubMed Google Scholar). Np-1 is part of a family that the receptor Np-2. In the Np-2 is class 3 which also the of axons that Np-2 Z. Full Full PubMed Scopus Google Scholar). have that Np-2 is also to bind VEGF165 and but not Np-1, Np-2 was also to with the form of the of which is in but the heparin-binding of the VEGF Z. Cohen T. G. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google have a and are to function as to VEGF165 when cells expressing either Np-1 or Np-2 but other VEGF receptors with VEGF165 S. S. G. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). was that form complexes with and that complexes T. 1999; Full Full PubMed Scopus Google Scholar, S. Z. M.L. 1999; Full Full PubMed Scopus Google Scholar). is that associate with cell to form complexes that VEGF indicating that Np-2 and possibly also Np-1 form complexes with the VEGFR-1 receptor and that the of complexes the binding of that are to bind a form that is not in cells that do not and Np-2 to function as receptors for class 3 that growing of axons the of the Z. Full Full PubMed Scopus Google Scholar, D.V. D.D. Full Full PubMed Scopus Google Scholar, Z. Full Full PubMed Scopus Google Scholar). These experiments that have that Np-1 and Np-2 function in as receptors for of the heparin-binding forms of the factor VEGF S. S. G. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). These experiments that the may a in in to their in the In the of Np-1 when it was that of the Np-1 in T. T. T. 1999; PubMed Google Scholar). In with it was that the Np-1 of endothelial cells S. J. Biol. 1999; PubMed Scopus Google but the of the binding of VEGF to Np-1 are not as In Np-2 receptors are and vascular D.V. S. S. D.D. Full Full PubMed Scopus Google Full Full PubMed Scopus Google Scholar). Nevertheless, the of vascular in not a for receptors in vascular because the of a may be with other signaling have not to to VEGF165 in cells expressing either Np-1 or Np-2 receptors and other of VEGF receptors S. S. G. Full Full PubMed Scopus Google Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). These that for the of VEGF the may have to associate with other and it was that binding of to Np-1 is not for of growth T. Full Full PubMed Scopus Google Scholar). was that form complexes with receptors to be to semaphorin T. 1999; Full Full PubMed Scopus Google Scholar, S. Z. M.L. 1999; Full Full PubMed Scopus Google Scholar). Our experiments and experiments indicate that in Np-2 form complexes with Our experiments also that Np-1 associate with was in a that was the of in which complexes Np-1 and VEGFR-1 G. J. Biol. Chem. Full Full PubMed Google which VEGFR-1 the binding of to Np-1 and Np-2 is The binding of VEGFR-1 to the may a that with is that to VEGFR-1, the bound in to in cells co-expressing both receptor and the of the The of VEGFR-1 binding may therefore be to the that heparin-like have the binding of VEGF165 to S. S. G. Full Full PubMed Scopus Google Scholar, S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google and Np-2 may be to form complexes to the of it is that VEGFR-1 to Np-2 to the binding of VEGF to have not to have to co-immunoprecipitated Np-2 or VEGFR-1 but we have of the cells or not to VEGF to the is that experiments because the of the was or because the complexes are to the the of the cells, the of complexes the we have To we have therefore to receptors that have cross-linked to the a T. K. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The we the the of but not to complex Np-2 and VEGFR-1 was or have the of complexes at The of complexes Np-2 and VEGFR-1 may to that is it may a to a in VEGFR-1 because of J. M.L. 1995; PubMed Scopus Google Scholar). In that the and of VEGFR-1 but the signaling S. J. T. U. S. PubMed Scopus Google Scholar). is the of VEGFR-1 is to the of is that the is for VEGF as to the of the may associate with to form a signaling is that Np-2 and Np-1 may participate in the of such a VEGFR-1 containing the of experiments we have that when epitope is the of the Np-2myc receptor most of its VEGF165binding ability. was that Np-1 and Np-2 form homodimers and heterodimers Z. Full Full PubMed Scopus Google Scholar). of such may be for binding of VEGF to The of epitope may with and with VEGF Interestingly, the VEGF165binding of Np-2myc was to in cells co-expressing VEGFR-1, because complex a of Np-2myc is Interestingly, the binding of Np-2 not the of because the of Np-2 to be from the as the of the experiments indicate that VEGFR-1 forms complexes with Np-2 and possibly also with The presence of VEGFR-1 the of VEGF to bind to Np-2. the function of complexes is In experiments indicate that in the of Np-2 VEGF binding to Np-2 and indicating that VEGF and bind to in the part of Np-2. The various forms of the growth factors belonging to the VEGF1 family (VEGF, PlGF, VEGF-B, VEGF-C, and VEGF-D) act as inducers and modulators of angiogenesis in vivo (1Neufeld G. Cohen T. Gengrinovitch S. Poltorak Z. FASEB J. 1999; 13: 9-22Crossref PubMed Scopus (3129) Google Scholar, 2Eriksson U. Alitalo K. Curr. Top. Microbiol. Immunol. 1999; 237: 41-57Crossref PubMed Scopus (151) Google Scholar, 3Persico M.G. Vincenti V. Dipalma T. Curr. Top. Microbiol. Immunol. 1999; 237: 31-40Crossref PubMed Scopus (145) Google Scholar). The active forms of the VEGF family members are synthesized as homodimers (4Leung D.W. Cachianes G. Kuang W.J. Goeddel D.V. Ferrara N. Science. 1989; 246: 1306-1309Crossref PubMed Scopus (4414) Google Scholar, 5Keck P.J. Hauser S.D. Krivi G. Sanzo K. Warren T. Feder J. Connolly D.T. Science. 1989; 246: 1309-1312Crossref PubMed Scopus (1794) Google Scholar) or as heterodimers with other VEGF family members such as PlGF (6DiSalvo J. Bayne M.L. Conn G. Kwok P.W. Trivedi P.G. Soderman D.D. Palisi T.M. Sullivan K.A. Thomas K.A. J. Biol. Chem. 1995; 270: 7717-7723Abstract Full Full PubMed Scopus Google Scholar). of the VEGF that angiogenesis is in containing a of the VEGF is therefore that the of of VEGF in vivo is for the of the N. K. PubMed Scopus Google Scholar, V. G. S. K. J. PubMed Scopus Google Scholar). forms of VEGF from to have (4Leung D.W. Cachianes G. Kuang W.J. Goeddel D.V. Ferrara N. Science. 1989; 246: 1306-1309Crossref PubMed Scopus (4414) Google Scholar, 5Keck P.J. Hauser S.D. Krivi G. Sanzo K. Warren T. Feder J. Connolly D.T. Science. 1989; 246: 1309-1312Crossref PubMed Scopus (1794) Google Scholar, Z. Cohen T. G. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, K.A. Ferrara N. J. Cachianes G. D.W. PubMed Scopus Google Scholar). These in the presence or the of the heparin-binding and to forms that in their and binding G. Cohen T. Poltorak Z. S. Gengrinovitch S. PubMed Scopus (145) Google Scholar). other VEGF family members such as PlGF and are also expressed in forms that in their binding ability. the of PlGF is in and a binding to not bind to V. G. M.G. Alitalo K. S. M.G. Google Scholar). VEGF bind to the receptors VEGFR-1 S. T. Google Scholar) and Google Scholar). The binding of VEGF to (1Neufeld G. Cohen T. Gengrinovitch S. Poltorak Z. FASEB J. 1999; 13: 9-22Crossref PubMed Scopus (3129) Google Scholar, PubMed Scopus Google Scholar, K. Ferrara N. Science. PubMed Scopus Google Scholar, S. N. T. G. Google Scholar, S. Full PubMed Scopus Google Scholar) and is with the of endothelial cell and in vivo angiogenesis PubMed Scopus Google Scholar, J. J. Biol. Chem. Full PubMed Google Scholar). the of VEGFR-1 not seem to result in the of cell or have G. Vincenti V. G. M.G. Google Scholar, PubMed Scopus Google Scholar). the of VEGFR-1 to cell J. J. Biol. Chem. Full PubMed Google Scholar, N. G. S. 1995; Google Scholar, G. U. J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, S. PubMed Google Scholar). Both receptors in and the because of endothelial cells not and do not form J. M.L. 1995; PubMed Scopus Google Scholar). In of the the VEGFR-1 receptor not the of endothelial cells in but the of from endothelial cells was J. M.L. 1995; PubMed Scopus Google Scholar). cells also of VEGF receptor a either or VEGFR-1 N. G. J. Biol. Chem. Full PubMed Google Scholar, S. G. J. Biol. Chem. Full PubMed Google Scholar). was that VEGF receptors of the endothelial cells are receptors that bind VEGF165 but not Cohen T. S. S. Gengrinovitch S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). experiments of and cell that of receptors S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The receptors from such cells VEGF165 and to be the products of the neuropilin-1 (Np-1) S. S. G. Full Full PubMed Scopus Google Scholar). was that the heparin-binding form of placenta growth factor and VEGF-B, members of the VEGF family of growth are also to bind to Np-1 S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, T. T. U. S. U. Alitalo K. J. Biol. Chem. 1999; Full Full PubMed Scopus Google Scholar). the of Np-1 as a VEGF receptor was it was that Np-1 in the as receptor for is a Np-1 that of growing of axons Z. Full Full PubMed Scopus Google Scholar, D.V. D.D. Full Full PubMed Scopus Google Scholar). was that is also to of endothelial cells S. J. Biol. 1999; PubMed Scopus Google Scholar). These indicate that signaling Np-1 angiogenesis and possibly the of the of the Np-1 in T. T. T. 1999; PubMed Google Scholar, T. T. T. Full Full PubMed Scopus Google Scholar, T. 1995; PubMed Google Scholar). Np-1 is part of a family that the receptor Np-2. In the Np-2 is class 3 which also the of axons that Np-2 Z. Full Full PubMed Scopus Google Scholar). have that Np-2 is also to bind VEGF165 and but not Np-1, Np-2 was also to with the form of the of which is in but the heparin-binding of the VEGF Z. Cohen T. G. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The have a and are to function as to VEGF165 when cells expressing either Np-1 or Np-2 but other VEGF receptors with VEGF165 S. S. G. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). was that form complexes with and that complexes T. 1999; Full Full PubMed Scopus Google Scholar, S. Z. M.L. 1999; Full Full PubMed Scopus Google Scholar). is that associate with cell to form complexes that VEGF indicating that Np-2 and possibly also Np-1 form complexes with the VEGFR-1 receptor and that the of complexes the binding of that are to bind a form that is not in cells that do not and Np-2 to function as receptors for class 3 that growing of axons the of the Z. Full Full PubMed Scopus Google Scholar, D.V. D.D. Full Full PubMed Scopus Google Scholar, Z. Full Full PubMed Scopus Google Scholar). These experiments that have that Np-1 and Np-2 function in as receptors for of the heparin-binding forms of the factor VEGF S. S. G. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). These experiments that the may a in in to their in the In the of Np-1 when it was that of the Np-1 in T. T. T. 1999; PubMed Google Scholar). In with it was that the Np-1 of endothelial cells S. J. Biol. 1999; PubMed Scopus Google but the of the binding of VEGF to Np-1 are not as In Np-2 receptors are and vascular D.V. S. S. D.D. Full Full PubMed Scopus Google Full Full PubMed Scopus Google Scholar). Nevertheless, the of vascular in not a for receptors in vascular because the of a may be with other signaling have not to to VEGF165 in cells expressing either Np-1 or Np-2 receptors and other of VEGF receptors S. S. G. Full Full PubMed Scopus Google Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). These that for the of VEGF the may have to associate with other and it was that binding of to Np-1 is not for of growth T. Full Full PubMed Scopus Google Scholar). was that form complexes with receptors to be to semaphorin T. 1999; Full Full PubMed Scopus Google Scholar, S. Z. M.L. 1999; Full Full PubMed Scopus Google Scholar). Our experiments and experiments indicate that in Np-2 form complexes with Our experiments also that Np-1 associate with was in a that was the of in which complexes Np-1 and VEGFR-1 G. J. Biol. Chem. Full Full PubMed Google which VEGFR-1 the binding of to Np-1 and Np-2 is The binding of VEGFR-1 to the may a that with is that to VEGFR-1, the bound in to in cells co-expressing both receptor and the of the The of VEGFR-1 binding may therefore be to the that heparin-like have the binding of VEGF165 to S. S. G. Full Full PubMed Scopus Google Scholar, S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google and Np-2 may be to form complexes to the of it is that VEGFR-1 to Np-2 to the binding of VEGF to have not to have to co-immunoprecipitated Np-2 or VEGFR-1 but we have of the cells or not to VEGF to the is that experiments because the of the was or because the complexes are to the the of the cells, the of complexes the we have To we have therefore to receptors that have cross-linked to the a T. K. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The we the the of but not to complex Np-2 and VEGFR-1 was or have the of complexes at The of complexes Np-2 and VEGFR-1 may to that is it may a to a in VEGFR-1 because of J. M.L. 1995; PubMed Scopus Google Scholar). In that the and of VEGFR-1 but the signaling S. J. T. U. S. PubMed Scopus Google Scholar). is the of VEGFR-1 is to the of is that the is for VEGF as to the of the may associate with to form a signaling is that Np-2 and Np-1 may participate in the of such a VEGFR-1 containing the of experiments we have that when epitope is the of the Np-2myc receptor most of its VEGF165binding ability. was that Np-1 and Np-2 form homodimers and heterodimers Z. Full Full PubMed Scopus Google Scholar). of such may be for binding of VEGF to The of epitope may with and with VEGF Interestingly, the VEGF165binding of Np-2myc was to in cells co-expressing VEGFR-1, because complex a of Np-2myc is Interestingly, the binding of Np-2 not the of because the of Np-2 to be from the as the of the experiments indicate that VEGFR-1 forms complexes with Np-2 and possibly also with The presence of VEGFR-1 the of VEGF to bind to Np-2. the function of complexes is In experiments indicate that in the of Np-2 VEGF binding to Np-2 and indicating that VEGF and bind to in the part of Np-2. Np-1 and Np-2 to function as receptors for class 3 that growing of axons the of the Z. Full Full PubMed Scopus Google Scholar, D.V. D.D. Full Full PubMed Scopus Google Scholar, Z. Full Full PubMed Scopus Google Scholar). These experiments that have that Np-1 and Np-2 function in as receptors for of the heparin-binding forms of the factor VEGF S. S. G. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). These experiments that the may a in in to their in the In the of Np-1 when it was that of the Np-1 in T. T. T. 1999; PubMed Google Scholar). In with it was that the Np-1 of endothelial cells S. J. Biol. 1999; PubMed Scopus Google but the of the binding of VEGF to Np-1 are not as In Np-2 receptors are and vascular D.V. S. S. D.D. Full Full PubMed Scopus Google Full Full PubMed Scopus Google Scholar). Nevertheless, the of vascular in not a for receptors in vascular because the of a may be with other signaling have not to to VEGF165 in cells expressing either Np-1 or Np-2 receptors and other of VEGF receptors S. S. G. Full Full PubMed Scopus Google Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). These that for the of VEGF the may have to associate with other and it was that binding of to Np-1 is not for of growth T. Full Full PubMed Scopus Google Scholar). was that form complexes with receptors to be to semaphorin T. 1999; Full Full PubMed Scopus Google Scholar, S. Z. M.L. 1999; Full Full PubMed Scopus Google Scholar). Our experiments and experiments indicate that in Np-2 form complexes with Our experiments also that Np-1 associate with was in a that was the of in which complexes Np-1 and VEGFR-1 G. J. Biol. Chem. Full Full PubMed Google Scholar). The which VEGFR-1 the binding of to Np-1 and Np-2 is The binding of VEGFR-1 to the may a that with is that to VEGFR-1, the bound in to in cells co-expressing both receptor and the of the The of VEGFR-1 binding may therefore be to the that heparin-like have the binding of VEGF165 to S. S. G. Full Full PubMed Scopus Google Scholar, S. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar, Z. Cohen T. G. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). VEGFR-1 and Np-2 may be to form complexes to the of it is that VEGFR-1 to Np-2 to the binding of VEGF to have not to have to co-immunoprecipitated Np-2 or VEGFR-1 but we have of the cells or not to VEGF to the is that experiments because the of the was or because the complexes are to the the of the cells, the of complexes the we have To we have therefore to receptors that have cross-linked to the a T. K. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The we the the of but not to complex Np-2 and VEGFR-1 was or have the of complexes at The of complexes Np-2 and VEGFR-1 may to that is it may a to a in VEGFR-1 because of J. M.L. 1995; PubMed Scopus Google Scholar). In that the and of VEGFR-1 but the signaling S. J. T. U. S. PubMed Scopus Google Scholar). is the of VEGFR-1 is to the of is that the is for VEGF as to the of the may associate with to form a signaling is that Np-2 and Np-1 may participate in the of such a VEGFR-1 containing In the of experiments we have that when epitope is the of the Np-2myc receptor most of its VEGF165binding ability. was that Np-1 and Np-2 form homodimers and heterodimers Z. Full Full PubMed Scopus Google Scholar). of such may be for binding of VEGF to The of epitope may with and with VEGF Interestingly, the VEGF165binding of Np-2myc was to in cells co-expressing VEGFR-1, because complex a of Np-2myc is Interestingly, the binding of Np-2 not the of because the of Np-2 to be from the as the of the To experiments indicate that VEGFR-1 forms complexes with Np-2 and possibly also with The presence of VEGFR-1 the of VEGF to bind to Np-2. the function of complexes is In experiments indicate that in the of Np-2 VEGF binding to Np-2 and indicating that VEGF and bind to in the part of Np-2.
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