The Interaction of Neuropilin-1 and Neuropilin-2 with Tyrosine-Kinase Receptors for VEGF

  • Gera Neufeld
  • Ofra Kessler
  • Yael Herzog

Abstract

The Neuropilin-1 (NRP 1) and Neuropilin-2 (NRP2) receptors were initially described as receptors for axon guidance factors belonging to the class-3 Semaphorin sub-family. Subsequently, it was found the Neuropilins also function as receptors for some forms of vascular endothelial growth factor (VEGF). VEGF165 binds to both NRP 1 and to NRP2 but VEGF121 does not bind to either of these receptors. VEGF145 on the other hand, binds to NRP2 but not to NRP1. Additional VEGF family members such as the heparin binding form of placenta growth factor (PIGF2) and VEGF-B bind to NRP 1, and it was also shown that both PIGF-2 and VEGFC bind to NRP2.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Takagi S, Hirata T, Agata K, Mochii M, Eguchi G, Fujisawa H. The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron 1991; 7(2):295-307.PubMedCrossRefGoogle Scholar
  2. 2.
    Fujisawa H, Takagi S, Hirata T. Growth-associated expression of a membrane protein, neuropilin, in Xenopus optic nerve fibers. Dev Neurosci 1995; 17(5-6):343-349.PubMedCrossRefGoogle Scholar
  3. 3.
    Raper JA. Semaphorins and their receptors in vertebrates and invertebrates. Curr Opin Neurobiol 2000; 10(1):88-94.PubMedCrossRefGoogle Scholar
  4. 4.
    Goodman CS, Kolodkin AL, Luo Y, Pueschel AW, Raper JA. Unified nomenclature for the semaphorins collapsins. Cell 1999; 97(5):551-552.CrossRefGoogle Scholar
  5. 5.
    Luo Y, Raible D, Raper JA. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 1993; 75(2):217-227.PubMedCrossRefGoogle Scholar
  6. 6.
    He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 1997; 90(4):739-751.PubMedCrossRefGoogle Scholar
  7. 7.
    Kolodkin AL, Levengood DV, Rowe EG, Tai YT, Giger RJ, Ginty DD. Neuropilin is a semaphorin III receptor. Cell 1997; 90(4):753-762.PubMedCrossRefGoogle Scholar
  8. 8.
    Giger RI, Urquhart ER, Gillespie SK, Levengood DV, Ginty DD, Kolodkin AL. Neuropilin2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity. Neuron 1998; 21(5):1079-1092.PubMedCrossRefGoogle Scholar
  9. 9.
    Takahashi T, Nakamura F, Jin Z, Kalb RG, Strittmatter SM. Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors. Nat Neurosci 1998; 1:487-493.PubMedCrossRefGoogle Scholar
  10. 10.
    Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999; 13:9-22.PubMedGoogle Scholar
  11. 11.
    Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 2001; I14(Pt 5):853-865.Google Scholar
  12. 12.
    Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodaysky I et al. VEGF145: A secreted VEGF form that binds to extracellular matrix. J Biol Chem 1997; 272:7151-7158.PubMedCrossRefGoogle Scholar
  13. 13.
    Park JE, Keller GA, Ferrara N. Vascular endothelial growth factor (VEGF) isoforms-Differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 1993; 4:1317-1326.PubMedGoogle Scholar
  14. 14.
    Carmeliet P, Ng YS, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I et al. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nature Med 1999; 5(5):495-502.PubMedCrossRefGoogle Scholar
  15. 15.
    Gitay-Goren H, Cohen T, Tessler S, Soker S, Gengrinovitch S, Rockwell P et al. Selective binding of VEGFI2I to one of the three VEGF receptors of vascular endothelial cells. J Biol Chem 1996; 271:5519-5523.PubMedCrossRefGoogle Scholar
  16. 16.
    Soker S, Fidder H, Neufeld G, Klagsbrun M. Characterization of novel VEGF binding proteins associated with tumor cells that bind VEGF165 but not VEGF121. J Biol Chem 1996; 271:5761-5767.PubMedCrossRefGoogle Scholar
  17. 17.
    Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform specific receptor for vascular endothelial growth factor. Cell 1998; 92:735-745.PubMedCrossRefGoogle Scholar
  18. 18.
    Migdal M, Huppertz B, Tessler S, Comforti A, Shibuya M, Reich R et al. Neuropilin-I is a placenta growth factor-2 receptor. J Biol Chem 1998; 273(35):22272-22278.PubMedCrossRefGoogle Scholar
  19. 19.
    Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G. Neuropilin-2 and Neuropilin-1 are receptors for 165-amino acid long form of vascular endothelial growth factor (VEGF) and of placenta growth factor-2, but only neuropilin-2 functions as a receptor for the 145 amino acid form of VEGF. J Biol Chem 2000; 275:18040-18045.PubMedCrossRefGoogle Scholar
  20. 20.
    Soker S, Gollamudi-Payne S, Fidder H, Charmahelli H, Klagsbrun M. Inhibition of vascular endothelial growth factor (VEGF) induced endothelial cell proliferation by a peptide corresponding to the exon-7 encoded domain of VEGF165. J Biol Chem 1997; 272(50):31582-31588.PubMedCrossRefGoogle Scholar
  21. 21.
    McDonnell JM. Surface plasmon resonance: towards an understanding of the mechanisms of biological molecular recognition. Curr Opin Chem Biol 2001; 5(5):572-577.PubMedCrossRefGoogle Scholar
  22. 22.
    Fuh G, Garcia KC, De Vos AM. The interaction of Neuropilin-1 with vascular endothelial growth factor and its receptor Flt-1. J Biol Chem 2000; 275(35):26690-26695.PubMedGoogle Scholar
  23. 23.
    Whitaker GB, Limberg BJ, Rosenbaum JS. Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF165 and VEGF121. J Biol Chem 2001; 276(27):25520-25531.PubMedCrossRefGoogle Scholar
  24. 24.
    Cai HB, Reed RR. Cloning and characterization of neuropilin-l-interacting protein: A PSD95/D1g/Z0-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. J Neurosci 1999; 19(15):6519-6527.PubMedGoogle Scholar
  25. 25.
    Yamada Y, Takakura N, Yasue H, Ogawa H, Fujisawa H, Suda T. Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis. Blood 2001; 97(6):1671-1678.PubMedCrossRefGoogle Scholar
  26. 26.
    Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M. Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. FASEB J 2000; 14(15):2532-2539.PubMedCrossRefGoogle Scholar
  27. 27.
    Devries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992; 255:989-991.CrossRefGoogle Scholar
  28. 28.
    Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H et al. Nucleotide sequence and expression of a novel human receptor type tyrosine kinase gene (fit) closely related to the fms family. Oncogene 1990; 5:519-524.PubMedGoogle Scholar
  29. 29.
    Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376:66-70.PubMedCrossRefGoogle Scholar
  30. 30.
    Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 1998; 95(16):9349-9354.PubMedCrossRefGoogle Scholar
  31. 31.
    Giuzman-Poltorak Z, Cohen T, Shibuya M, Neufeld G. Vascular endothelial growth factor receptor-1 and neuropilin-2 form complexes. J Biol Chem 2001; 276(22):18688-18694.CrossRefGoogle Scholar
  32. 32.
    Bagnard D, Vaillant C, Khuth ST, Dufay N, Lohrum M, Puschel AW et al. Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor. J Neurosci 2001; 21(10):3332-3341.PubMedGoogle Scholar
  33. 33.
    Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. Proc Natl Acad Sci USA 2000; 97(6):2573-2578.PubMedCrossRefGoogle Scholar
  34. 34.
    Miao HQ, Klagsbrun M. Neuropilin is a mediator of angiogenesis. Cancer Metastasis Rev 2000; 19(1-2):29-37.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Gera Neufeld
    • 1
  • Ofra Kessler
  • Yael Herzog
    • 1
  1. 1.Department of BiologyTechnion, Israel Institute of TechnologyHaifaIsrael

Personalised recommendations