Semaphorin Signaling in Vascular and Tumor Biology

  • Gera Neufeld
  • Tali Lange
  • Asya Varshavsky
  • Ofra Kessler
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 600)


The neuropilins were originally characterized as cell membrane receptors that bind axon guidance factors belonging to the class-3 semaphorin subfamily. To transduce semaphorin signals, they form complexes with members of the plexin receptor family in which neuropilins serve as the ligand binding components and the plexins as the signal transducing components. The neuropilins were subsequently found to double as receptors for specific heparin binding splice forms of vascular endothelial growth factor (VEGF), and to be expressed on endothelial cells. This finding suggested that semaphorins may function as modulators of angiogenesis. It was recently found that several types of semaphorins such as semaphorin-3F function as inhibitors of angiogenesis while others, most notably semaphorin-4D, function as angiogenic factors. Furthermore, semaphorins such as semaphorin-3F and semaphorin-3B have been characterized as tumor suppressors and have been found to exert direct effects upon tumor cells. In this chapter we cover recent developments in this rapidly developing field of research


Vascular Endothelial Growth Factor Splice Form Vascular Endothelial Growth Factor Signaling Sema Domain Vascular Endothelial Growth Factor Family 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Luo Y, Raible D, Raper JA. Collapsin: A protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 1993; 75:217–227.PubMedGoogle Scholar
  2. 2.
    Goodman CS, Kolodkin AL, Luo Y et al. Unified nomenclature for the semaphorins collapsins. Cell 1999; 97:551–552.Google Scholar
  3. 3.
    Gherardi E, Love CA, Esnouf RM et al. The sema domain. Curr Opin Struct Biol 2004; 14:669–678.PubMedGoogle Scholar
  4. 4.
    Wang X, Kumanogoh A, Watanabe C et al. Functional soluble CD100/Sema4D released from activated lymphocytes: Possible role in normal and pathologic immune responses. Blood 2001; 97:3498–3504.PubMedGoogle Scholar
  5. 5.
    Isbister CM, O’connor TP. Mechanisms of growth cone guidance and motility in the developing grasshopper embryo. J Neurobiol 2000; 44:271–280.PubMedGoogle Scholar
  6. 6.
    Shirvan A, Ziv I, Fleminger G et al. Semaphorins as mediators of neuronal apoptosis. J Neurochem 1999; 73:961–971.PubMedGoogle Scholar
  7. 7.
    Bagnard D, Sainturet N, Meyronet D et al. Differential MAP kinases activation during Semaphorin3A-induced repulsion or apoptosis of neural progenitor cells. Mol Cell Neurosci 2004; 25:722–731.PubMedGoogle Scholar
  8. 8.
    Tamamaki N, Fujimori K, Nojyo Y et al. Evidence that Sema3A and Sema3F regulate the migration of GABAergic neurons in the developing neocortex. J Comp Neurol 2003; 455:238–248.PubMedGoogle Scholar
  9. 9.
    Bagnard D, Vaillant C, Khuth ST 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; 21:3332–3341.PubMedGoogle Scholar
  10. 10.
    Brambilla E, Constantin B, Drabkin H et al. Semaphorin SEMA3F localization in malignant human lung and cell lines: A suggested role in cell adhesion and cell migration. Am J Pathol 2000; 156:939–950.PubMedGoogle Scholar
  11. 11.
    Barberis D, Artigiani S, Casazza A et al. Plexin signaling hampers integrin-based adhesion, leading to Rho-kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility. Faseb J 2004; 18:592–594.PubMedGoogle Scholar
  12. 12.
    Takahashi T, Fournier A, Nakamura F et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 1999; 99:59–69.PubMedGoogle Scholar
  13. 13.
    Gu C, Yoshida Y, Livet J et al. Semaphorin 3E and Plexin-D1 control vascular pattern independently of neuropilins. Science 2005; 307:265–268.PubMedGoogle Scholar
  14. 14.
    Tamagnone L, Artigiani S, Chen H et al. Plexins are a large family of receptors for transmembrane, screted, and GPI-Anchored semaphorins in vertebrates. Cell 1999; 99:71–80.PubMedGoogle Scholar
  15. 15.
    Takagi S, Hirata T, Agata K et al. The A5 antigen, a candilate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron 1991; 7:295–307.PubMedGoogle Scholar
  16. 16.
    Fujisawa H, Takagi S, Hirata T. Growth-Associated expression of a membrane protein, neuropilin, in Xenopus optic nerve fibers. Dev Neurosci 1995; 17:343–349.PubMedGoogle Scholar
  17. 17.
    Kolodkin AL, Levengood DV, Rowe EG et al. Neuropilin is a semaphorin III receptor. Cell 1997; 90:753–762.PubMedGoogle Scholar
  18. 18.
    Chen H, Chedotal A, He Z et al. Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 1997; 19:547–559.PubMedGoogle Scholar
  19. 19.
    Giger RJ, Urquhart ER, Gillespie SK et al. Neuropilin-2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity. Neuron 1998; 21:1079–1092.PubMedGoogle Scholar
  20. 20.
    He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 1997; 90:739–751.PubMedGoogle Scholar
  21. 21.
    Gu C, Limberg BJ, Whitaker GB et al. Characterization of neuropilin-1 structural features that confer binding to semaphorin 3A and vascular endothelial growth factor 165. J Biol Chem 2002; 277:18069–18076.PubMedGoogle Scholar
  22. 22.
    Nakamura F, Tanaka M, Takahashi T et al. Neuropilin-1 extracellular domains mediate Semaphorin D/III-induced growth cone collapse. Neuron 1998; 21:1093–1100.PubMedGoogle Scholar
  23. 23.
    Negishi M, Oinuma I, Katoh H. Plexins: Axon guidance and signal transduction. Cell Mol Life Sci 2005; 62(12):1363–1371.PubMedGoogle Scholar
  24. 24.
    Gutmann-Raviv N, Kessler O, Shraga-Heled N et al. The neuropilins and their roll in tumorigenesis and tumor progression. Cancer Lett 2006; 231:1–11.Google Scholar
  25. 25.
    Artigiani S, Conrotto P, Fazzari P et al. Plexin-B3 is a functional receptor for semaphorin 5A. Embo Rep 2004; 5:710–714.PubMedGoogle Scholar
  26. 26.
    Toyofuku T, Zhang H, Kumanogoh A et al. Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-tack and vascular endothelial growth factor receptor type 2. Genes Dev 2004; 18:435–447.PubMedGoogle Scholar
  27. 27.
    Takahashi T, Strittmatter SM. PlexinA1 autoinhibition by the plexin sema domain. Neuron 2001; 29:429–439.PubMedGoogle Scholar
  28. 28.
    Comoglio PM, Trusolino L. Invasive growth: From development to metastasis. J Clin Invest 2002; 109:857–862.PubMedGoogle Scholar
  29. 29.
    Oinuma I, Ishikawa Y, Katoh H et al. The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science 2004; 305:862–865.PubMedGoogle Scholar
  30. 30.
    Zhang Z, Vuori K, Wang H et al. Integrin activation by R-ras. Cell 1996; 85:61–69.PubMedGoogle Scholar
  31. 31.
    Zanata SM, Hovatta I, Rohm B et al. Antagonistic effects of Rnd1 and RhoD GTPases regulate receptor activity in Semaphorin 3A-induced cytoskeletal collapse. J Neurosci 2002; 22:471–477.PubMedGoogle Scholar
  32. 32.
    Perrot V, Vazquez-Prado J, Gutkind JS. Plexin B regulates Rho through the guanine nucleotide exchange factors Leukemia-associated RhoGEF (LARG) and PDZ-RhoGEF. J Biol Chem 2002; 278:26111–26119.Google Scholar
  33. 33.
    Aurandt J. Vikis HG, Gutkind JS et al. The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, larg. Proc Natl Acad Sci USA 2002; 99:12085–12090.PubMedGoogle Scholar
  34. 34.
    Hall A. Rho GTPases and the control of cell behaviour. Biochem Soc Trans 2005; 33:891–895.PubMedGoogle Scholar
  35. 35.
    Arimura N, Menager C, Kawano Y et al. Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones. Mol Cell Biol 2005; 25: 9973–9984.PubMedGoogle Scholar
  36. 36.
    Harden N, Lee J, Loh HY et al. A Drosophila homolog of the Rac-And Cdc42-activated serine/threonine kinase PAK is a potential focal adhesion and focal complex protein that colocalizes with dynamic actin structures. Mol Cell Biol 1996; 16: 1896–1908.PubMedGoogle Scholar
  37. 37.
    Mitsui N, Inatome R, Takahashi S et al. Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling. EMBO J 2002; 21:3274–3285.PubMedGoogle Scholar
  38. 38.
    Gu YJ, Ihara Y. Accelerated publication—Evidence that collapsin response mediator protein-2 is involved in the dynamics of microtubules. J Biol Chem 2000; 275:17917–17920.PubMedGoogle Scholar
  39. 39.
    Brown M, Jacobs T, Eickholt B et al. Alpha2-chimaerin, cyclin-dependent Kinase 5/P35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse. J Neurosci 2004; 24:8994–9004.PubMedGoogle Scholar
  40. 40.
    Sasaki Y, Cheng C, Uchida Y et al. Fyn and Cdk5 mediate Semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron 2002; 35:907.PubMedGoogle Scholar
  41. 41.
    Terman JR, Mao T, Pasterkamp RJ et al. MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion. Cell 2002; 109:887–900.PubMedGoogle Scholar
  42. 42.
    Pasterkamp RJ, Dai HN, Terman JR et al. MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat. Mol Cell Neurosci 2006; 31:52–69.PubMedGoogle Scholar
  43. 43.
    Neufeld G, Cohen T, Gengrinovitch S et al. Vascular endothelial growth factor (VEGF) and its receptors. Faseb J 1999; 13:9–22.PubMedGoogle Scholar
  44. 44.
    Terman BI, Dougher-Vermazen M, Carrion ME et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 1992; 187:1579–1586.PubMedGoogle Scholar
  45. 45.
    Shibuya M. Vascular endothelial growth factor receptor-2: Its unique signaling and specific ligand, VEGF-E. Cancer Sci 2003; 94:751–756.PubMedGoogle Scholar
  46. 46.
    Devries C, Escobedo JA, Ueno H et al. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992;255:989–991.Google Scholar
  47. 47.
    Fong GH, Rossant J, Gertsenstein M et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376:66–70.PubMedGoogle Scholar
  48. 48.
    Hiratsuka S, Minowa O, Kuno J et al. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 1998; 95:9349–9354.PubMedGoogle Scholar
  49. 49.
    Luttun A, Tjwa M, Moons L et al. Revascularization of ischemic tissues by PIGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 2002; 8:831–840.PubMedGoogle Scholar
  50. 50.
    Gitay-Goren H, Cohen T, Tessler S et al. Selective binding of VEGF121 to one of the three VEGF receptors of vascular endothelial cells. J Biol Chem 1996; 271:5519–5523.PubMedGoogle Scholar
  51. 51.
    Soker S, Takashima S, Miao HQ et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform specific receptor for vascular endothelial growth factor. Cell 1998; 92:735–745.PubMedGoogle Scholar
  52. 52.
    Gluzman-Poltorak Z, Cohen T, Herzog Y et al. 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.PubMedGoogle Scholar
  53. 53.
    Makinen T, Olofsson B, Karpanen T et al. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem 1999; 274:21217–21222.PubMedGoogle Scholar
  54. 54.
    Migdal M, Huppertz B, Tessler S et al. Neuropilin-1 is a placenta growth factor-2 receptor. J Biol Chem 1998; 273:22272–22278.PubMedGoogle Scholar
  55. 55.
    Tammeda T, Enholm B, Alitalo K et al. The biology of vascular endothelial growth factors. Cardiovasc Res 2005; 65:550–563.Google Scholar
  56. 56.
    Veikkola T, Jussila L, Makinen T et al. Signaling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. Embo J 2001; 20:1223–1231.PubMedGoogle Scholar
  57. 57.
    Kaipainen A, Korhonen J, Mustonen T et al. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci USA 1995; 92:3566–3570.PubMedGoogle Scholar
  58. 58.
    Kukk E, Lymboussaki A, Taira S et al. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 1996; 122:3829–3837.PubMedGoogle Scholar
  59. 59.
    Karkkainen MJ, Saaristo A, Jussila L et al. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci USA 2001; 98:12677–12682.PubMedGoogle Scholar
  60. 60.
    Yuan L, Moyon D, Pardanaud L et al. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 2002; 129:4797–4806.PubMedGoogle Scholar
  61. 61.
    Kawasaki T, Kitsukawa T, Bekku Y et al. A requirement for neuropilin-1 in embryonic vessel formation. Development 1999; 126:4895–4902.PubMedGoogle Scholar
  62. 62.
    Giger RJ, Cloutier JF, Sahay A et al. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron 2000; 25:29–41.PubMedGoogle Scholar
  63. 63.
    Shen J, Samul R, Zimmer J et al. Deficiency of Neuropilin 2 suppresses VEGF-induced retinal neovascularization. Mol Med 2004; 10:12–18.PubMedGoogle Scholar
  64. 64.
    Takashima S, Kitakaze M, Asakura M et al. Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Proc Natl Acad Sci USA 2002; 99:3657–3662.PubMedGoogle Scholar
  65. 65.
    Shalaby F, Rossant J, Yamaguchi TP et al. Failure of blood-island formation and vasculogenesis in Flk-1-Deficient mice. Nature 1995; 376:62–66.PubMedGoogle Scholar
  66. 66.
    Miao HQ, Soker S, Feiner L et al. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility. Functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 1999; 146:233–242.PubMedGoogle Scholar
  67. 67.
    Gluzman-Poltorak Z, Cohen T, Shibuya M et al. Vascular endothelial growth factor receptor-1 and neuropilin-2 form complexes. J Biol Chem 2001; 276:18688–18694.PubMedGoogle Scholar
  68. 68.
    Gu C, Rodriguez ER, Reimert DV et al. neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell 2003; 5:45–57.PubMedGoogle Scholar
  69. 69.
    Bates D, Taylor GI, Minichiello J et al. Neurovascular congruence results from a shared patterning mechanism that utilizes Semaphorin3A and Neuropilin-1. Dev Biol 2003; 255:77–98.PubMedGoogle Scholar
  70. 70.
    Serini G, Valdembri D, Zanivan S et al. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature 2003; 424:391–397.PubMedGoogle Scholar
  71. 71.
    Kessler O, Shraga-Heled N, Lange T et al. Semaphorin-3F is an inhibitor of tumor angiogenesis. Cancer Res 2004; 64:1008–1015.PubMedGoogle Scholar
  72. 72.
    Bielenberg DR, Hida Y, Shimizu A et al. Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype. J Clin Invest 2004; 114:1260–1271.PubMedGoogle Scholar
  73. 73.
    Xiang RH, Hensel CH, Garcia DK et al. Isolation of the human semaphorin III/F gene (SEMA3F) at chromosome 3p21, a region deleted in lung cancer. Genomics 1996; 32:39–48.PubMedGoogle Scholar
  74. 74.
    Sekido Y, Bader S, Latif F et al. Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. Proc Natl Acad Sci USA 1996; 93:4120–4125.PubMedGoogle Scholar
  75. 75.
    Xiang R, Davalos AR, Hensel CH et al. Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice. Cancer Res 2002; 62:2637–2643.PubMedGoogle Scholar
  76. 76.
    Nasarre P, Constantin B, Rouhaud L et al. Semaphorin SEMA3F and VEGF have opposing effects on cell attachment and spreading. Neoplasia 2003; 5:83–92.PubMedGoogle Scholar
  77. 77.
    Nasarre P, Kusy S, Constantin B et al. Semaphorin SEMA3F has a repulsing activity on breast cancer cells and inhibits E-Cadherin-mediated cell adhesion. Neoplasia 2005; 7:180–189.PubMedGoogle Scholar
  78. 78.
    Marsit CJ, Wiencke JK, Liu M et al. The race associated allele of semaphorin 3B (SEMA3B) T4151 and its role in lung cancer in African-Americans and Latino-Americans. Carcinogenesis 2005; 26:1446–1449.PubMedGoogle Scholar
  79. 79.
    Kuroki T, Trapasso F, Yendamuri S et al. Allelic loss on chromosome 3p21.3 and promoter hypermethylation of Semaphorin 3B in nonsmall cell lung cancer. Cancer Res 2003; 63:3352–3355.PubMedGoogle Scholar
  80. 80.
    Tomizawa Y, Sekido Y, Kondo M et al. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci USA 2001; 98:13954–13959.PubMedGoogle Scholar
  81. 81.
    Tse C, Xiang RH, Bracht T et al. Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res 2002; 62:542–546.PubMedGoogle Scholar
  82. 82.
    Castro-Rivera E, Ran S, Thorpe P et al. Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci USA 2004; 101:11432–11437.PubMedGoogle Scholar
  83. 83.
    Julien F, Bechara A, Fiore R et al. Dual functional activity of Semaphorin 3B is required for positioning the anterior commissure. Neuron 2005; 48:63–75.PubMedGoogle Scholar
  84. 84.
    Van Der WL, Adams DJ, Harris LW et al. Null and conditional semaphorin 3B alleles using a flexible puroDeltatk loxP/FRT vector. Genesis 2005; 41:171–178.Google Scholar
  85. 85.
    Takahashi T, Nakamura F, Jin Z et al. Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors. Nat Neurosci 1998; 1:487–493.PubMedGoogle Scholar
  86. 86.
    Gitler AD, Lu MM, Epstein JA. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev Cell 2004; 7:107–116.PubMedGoogle Scholar
  87. 87.
    Feiner L, Webber AL, Brown CB et al. Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption. Development 2001; 128:3061–3070.PubMedGoogle Scholar
  88. 88.
    Torres-Vazquez J, Gitler AD, Fraser SD et al. Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev Cell 2004; 7:117–123.PubMedGoogle Scholar
  89. 89.
    Christensen CR, Klingelhofer J, Tarabykina S et al. Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines. Cancer Res 1998; 58:1238–1244.PubMedGoogle Scholar
  90. 90.
    Christensen C, Ambartsumian N, Gilestro G et al. Proteolytic processing converts the repelling signal Sema3E into an inducer of invasive growth and lung metastasis. Cancer Res 2005; 65:6167–6177.PubMedGoogle Scholar
  91. 91.
    Kikutani H, Kumanogoh A. Semaphorins in interactions between T cells and antigen-presenting cells. Nat Rev Immunol 2003; 3:159–167.PubMedGoogle Scholar
  92. 92.
    Zhang YW, Vande Woude GF. HGF/SF-met signaling in the control of branching morphogenesis and invasion. J Cell Biochem 2003; 88:408–417.PubMedGoogle Scholar
  93. 93.
    Van DV, Taher TE, Derksen PW et al. The hepatocyte growth factor/Met pathway in development, tumorigenesis, and B-cell differentiation. Adv Cancer Res 2000; 79:39–90.Google Scholar
  94. 94.
    Giordano S, Corso S, Conrotto P et al. The Semaphorin 4D receptor controls invasive growth by coupling with met. Nat Cell Biol 2002; 4:720–724.PubMedGoogle Scholar
  95. 95.
    Conrotto P, Corso S, Gamberini S et al. Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene 2004; 23:5131–5137.PubMedGoogle Scholar
  96. 96.
    Bussolino F, Di Renzo MF, Ziche M et al. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol 1992; 119:629–641.PubMedGoogle Scholar
  97. 97.
    Grant DS, Kleinman HK, Goldberg ID et al. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci USA 1993; 90:1937–1941.PubMedGoogle Scholar
  98. 98.
    Conrotto P, Valdembri D, Corso S et al. Sema4D induces angiogenesis through met recruitment by Plexin B1. Blood 2005; 105:4321–4329.PubMedGoogle Scholar
  99. 99.
    Swiercz JM, Kuner R, Offermanns S. Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol 2004; 165:869–880.PubMedGoogle Scholar
  100. 100.
    Peles E, Yarden Y. Neu and its ligands: From an oncogene to neural factors. Bioessays 1993; 15:815–824.PubMedGoogle Scholar
  101. 101.
    Basile JR, Barac A, Zhu T et al. Class IV semaphorins promote angiogenesis by stimulating Rho-initiated pathways through plexin-B. Cancer Res 2004; 64:5212–5224.PubMedGoogle Scholar
  102. 102.
    Woodhouse EC, Fisher A, Bandle RW et al. Drosophila screening model for metastasis: Semaphorin 5c is required for l(2)gl cancer phenotype. Proc Natl Acad Sci USA 2003; 100:11463–11468.PubMedGoogle Scholar
  103. 103.
    Inagaki S, Furuyama T, Iwahashi Y. Identification of a member of mouse semaphorin family. Febs Lett 1995; 370:269–272.PubMedGoogle Scholar
  104. 104.
    Furuyama T, Inagaki S, Kosugi A et al. Identification of a novel transmembrane semaphorin expressed on lymphocytes. J Biol Chem 1996; 271:33376–33381.PubMedGoogle Scholar
  105. 105.
    Fiore R, Rahim B, Christoffels VM et al. Inactivationof the sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system. Mol Cell Biol 2005; 25:2310–2319.PubMedGoogle Scholar
  106. 106.
    Correa RG, Sasahara RM, Bengtson MH et al. Human semaphorin 6B [(HSA)SEMA6B], a novel human class 6 semaphorin gene: Alternative splicing and all-trans-retinoic acid-dependent downregulation in glioblastoma cell lines. Genomics 2001; 73:343–348.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Gera Neufeld
    • 1
  • Tali Lange
  • Asya Varshavsky
  • Ofra Kessler
  1. 1.Cancer and Vascular Biology Research Center, Rappaport Research Institute in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, TechnionIsrael Institute of TechnologyHaifaIsrael

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