Signaling via vascular endothelial growth factor receptors

Experimental Cell Research

Volumn 253, Issue 1, 1999, Pages 117-130

  Petrova, Tatiana V ^a   Makinen, Taija ^a   Alitalo, Kari ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Angiogenesis; Endothelial cells; Receptor tyrosine kinases; Signal transduction; VEGF; VEGF receptors

Indexed keywords

COLLAGENASE; INTEGRIN; NEUROPILIN; NITRIC OXIDE SYNTHASE; PLATELET DERIVED GROWTH FACTOR BB; PROTEIN BCL 2; THROMBOPLASTIN; TISSUE PLASMINOGEN ACTIVATOR; UROKINASE; UROKINASE RECEPTOR; VASCULOTROPIN RECEPTOR;

ANGIOGENESIS; ANIMAL CELL; CELL COMMUNICATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

EID: 0033604614     PISSN: 00144827     EISSN: None     Source Type: Journal    
DOI: 10.1006/excr.1999.4707     Document Type: Article

References (173)

1. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1:1995;27-31.
2. Ruegg C., Yilmaz A., Bieler G., Bamat J., Chaubert P., Lejeune F. J. Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. Nat. Med. 4:1998;408-414.
3. Bergers G., Javaherian K., Lo K. M., Folkman J., Hanahan D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science. 284:1999;808-812.
4. Isner J. M., Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J. Clin. Invest. 103:1999;1231-1236.
5. Folkman J., Shing Y. Angiogenesis. J. Biol. Chem. 267:1992;10931-10934.
6. Suri C., Jones P. F., Patan S., Bartunkova S., Maisonpierre P. C., Davis S., Sato T. N., Yancopoulos G. D. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 87:1996;1171-1180.
7. Davis S., Aldrich T. H., Jones P. F., Acheson A., Compton D. L., Jain V., Ryan T. E., Bruno J., Radziejewski C., Maisonpierre P. C., Yancopoulos G. D. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell. 87:1996;1161-1169.
8. Maisonpierre P. C., Suri C., Jones P. F., Bartunkova S., Wiegand S. J., Radziejewski C., Compton D., McClain J., Aldrich T. H., Papadopoulos N., Daly T. J., Davis S., Sato T. N., Yancopoulos G. D. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 277:1997;55-60.
9. Risau W. Mechanisms of angiogenesis. Nature. 386:1997;671-674.
10. O'Reilly M. S., Holmgren L., Shing Y., Chen C., Rosenthal R. A., Moses M., Lane W. S., Cao Y., Sage E. H., Folkman J. Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 79:1994;315-328.
11. O'Reilly M. S., Boehm T., Shing Y., Fukai N., Vasios G., Lane W. S., Flynn E., Birkhead J. R., Olsen B. R., Folkman J. Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell. 88:1997;277-285.
12. Ferrara N., Clapp C., Weiner R. The 16K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells. Endocrinology. 129:1991;896-900.
13. Good D. J., Polverini P. J., Rastinejad F., Le Beau M. M., Lemons R. S., Frazier W. A., Bouck N. P. A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc. Natl. Acad. Sci. USA. 87:1990;6624-6628.
14. Maione T. E., Gray G. S., Petro J., Hunt A. J., Donner A. L., Bauer S. I., Carson H. F., Sharpe R. J. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science. 247:1990;77-79.
15. Neufeld G., Cohen T., Gengrinovitch S., Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13:1999;9-22.
16. Veikkola T., Alitalo K. VEGFs, receptors and angiogenesis. Semin. Cancer. Biol. 9:1999;211-220.
17. Maglione D., Guerriero V., Viglietto G., Delli-Bovi P., Persico M. G. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc. Natl. Acad. Sci. USA. 88:1991;9267-9271.
18. Olofsson B., Pajusola K., Kaipainen A., von Euler G., Joukov V., Saksela O., Orpana A., Pettersson R. F., Alitalo K., Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc. Natl. Acad. Sci. USA. 93:1996;2576-2581.
19. Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 15:1996;290-298.
20. Lee J., Gray A., Yuan J., Luoh S. M., Avraham H., Wood W. I. Vascular endothelial growth factor-related protein: A ligand and specific activator of the tyrosine kinase receptor Flt4. Proc. Natl. Acad. Sci. USA. 93:1996;1988-1992.
21. Orlandini M., Marconcini L., Ferruzzi R., Oliviero S. Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family. Proc. Natl. Acad. Sci. USA. 93:1996;11675-11680.
22. Achen M. G., Jeltsch M., Kukk E., Makinen T., Vitali A., Wilks A. F., Alitalo K., Stacker S. A. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc. Natl. Acad. Sci. USA. 95:1998;548-553.
23. Ogawa S., Oku A., Sawano A., Yamaguchi S., Yazaki Y., Shibuya M. A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J. Biol. Chem. 273:1998;31273-31282.
24. Wise L. M., Veikkola T., Mercer A. A., Savory L. J., Fleming S. B., Caesar C., Vitali A., Makinen T., Alitalo K., Stacker S. A. Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. Proc. Natl. Acad. Sci. USA. 96:1999;3071-3076.
25. Meyer M., Clauss M., Lepple-Wienhues A., Waltenberger J., Augustin H. G., Ziche M., Lanz C., Buttner M., Rziha H. J., Dehio C. A novel vascular endothelial growth factor encoded by Orf virus, VEGF- E, mediates angiogenesis via signaling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. EMBO J. 18:1999;363-374.
26. Soker S., Takashima S., Miao H. Q., Neufeld G., Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 92:1998;735-745.
27. Joukov V., Kaipainen A., Jeltsch M., Pajusola K., Olofsson B., Kumar V., Eriksson U., Alitalo K. Vascular endothelial growth factors VEGF-B and VEGF-C. J. Cell. Physiol. 173:1997;211-215.
28. Ferrara N., Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr. Rev. 18:1997;4-25.
29. Ferrara N. Vascular endothelial growth factor: Molecular and biological aspects. Curr. Top. Microbiol. Immunol. 237:1999;1-30.
30. de Vries C., Escobedo J. A., Ueno H., Houck K., Ferrara N., Williams L. T. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 255:1992;989-991.
31. Terman B. I., Dougher-Vermazen M., Carrion M. E., Dimitrov D., Armellino D. C., Gospodarowicz D., Bohlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem. Biophys. Res. Commun. 187:1992;1579-1586.
32. Olofsson B., Korpelainen E., Pepper M. S., Mandriota S. J., Aase K., Kumar V., Gunji Y., Jeltsch M. M., Shibuya M., Alitalo K., Eriksson U. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc. Natl. Acad. Sci. USA. 95:1998;11709-11714.
33. Migdal M., Huppertz B., Tessler S., Comforti A., Shibuya M., Reich R., Baumann H., Neufeld G. Neuropilin-1 is a placenta growth factor-2 receptor. J. Biol. Chem. 273:1998;22272-22278.
34. Makinen T., Olofsson B., Karpanen T., Hellman U., Soker S., Klagsbrun M., Eriksson U., Alitalo K. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J. Biol. Chem. 274:1999;21217-21222.
35. Hauser S., Weich H. A. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors. 9:1993;259-268.
36. Cao Y., Ji W. R., Qi P., Rosin A. Placenta growth factor: Identification and characterization of a novel isoform generated by RNA alternative splicing. Biochem. Biophys. Res. Commun. 235:1997;493-498.
37. Olofsson B., Pajusola K., von Euler G., Chilov D., Alitalo K., Eriksson U. Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform. J. Biol. Chem. 271:1996;19310-19317.
38. Joukov V., Sorsa T., Kumar V., Jeltsch M., Claesson-Welsh L., Cao Y., Saksela O., Kalkkinen N., Alitalo K. Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 16:1997;3898-3911.
39. van der Geer P., Hunter T., Lindberg R. A. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu. Rev. Cell. Biol. 10:1994;251-337.
40. Shibuya M. Role of VEGF-flt receptor system in normal and tumor angiogenesis. Adv. Cancer Res. 67:1995;281-316.
41. Klagsbrun M., D'Amore P. A. Vascular endothelial growth factor and its receptors. Cytokine Growth Factor Rev. 7:1996;259-270.
42. Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 5:1990;519-524.
43. Finnerty H., Kelleher K., Morris G. E., Bean K., Merberg D. M., Kriz R., Morris J. C., Sookdeo H., Turner K. J., Wood C. R. Molecular cloning of murine FLT and FLT4. Oncogene. 8:1993;2293-2298.
44. Yamane A., Seetharam L., Yamaguchi S., Gotoh N., Takahashi T., Neufeld G., Shibuya M. A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1). Oncogene. 9:1994;2683-2690.
45. Choi K., Wall C., Hanratty R., Keller G. Isolation of a gene encoding a novel receptor tyrosine kinase from differentiated embryonic stem cells. Oncogene. 9:1994;1261-1266.
46. Terman B. I., Carrion M. E., Kovacs E., Rasmussen B. A., Eddy R. L., Shows T. B. Identification of a new endothelial cell growth factor receptor tyrosine kinase. Oncogene. 6:1991;1677-1683.
47. Matthews W., Jordan C. T., Gavin M., Jenkins N. A., Copeland N. G., Lemischka I. R. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Proc. Natl. Acad. Sci. USA. 88:1991;9026-9030.
48. Millauer B., Wizigmann-Voos S., Schnurch H., Martinez R., Moller N. P., Risau W., Ullrich A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 72:1993;835-846.
49. Oelrichs R. B., Reid H. H., Bernard O., Ziemiecki A., Wilks A. F. NYK/FLK-1: A putative receptor protein tyrosine kinase isolated from E10 embryonic neuroepithelium is expressed in endothelial cells of the developing embryo. Oncogene. 8:1993;11-18.
50. Sarzani R., Arnaldi G., De Pirro R., Moretti P., Schiaffino S., Rappelli A. A novel endothelial tyrosine kinase cDNA homologous to platelet-derived growth factor receptor cDNA. Biochem. Biophys. Res. Commun. 186:1992;706-714.
51. Eichmann A., Marcelle C., Breant C., Le Douarin N. M. Two molecules related to the VEGF receptor are expressed in early endothelial cells during avian embryonic development. Mech. Dev. 42:1993;33-48.
52. Sumoy L., Keasey J. B., Dittman T. D., Kimelman D. A role for notochord in axial vascular development revealed by analysis of phenotype and the expression of VEGR-2 in zebrafish flh and ntl mutant embryos. Mech. Dev. 63:1997;15-27.
53. Galland F., Karamysheva A., Mattei M. G., Rosnet O., Marchetto S., Birnbaum D. Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene. Genomics. 13:1992;475-478.
54. Aprelikova O., Pajusola K., Partanen J., Armstrong E., Alitalo R., Bailey S. K., McMahon J., Wasmuth J., Huebner K., Alitalo K. FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter. Cancer Res. 52:1992;746-748.
55. Terman B. I., Jani-Sait S., Carrion M. E., Shows T. B. The KDR gene maps to human chromosome 4q31.2-q32, a locus which is distinct from locations for other type III growth factor receptor tyrosine kinases. Cytogenet. Cell Genet. 60:1992;214-215.
56. Rosnet O., Stephenson D., Mattei M. G., Marchetto S., Shibuya M., Chapman V. M., Birnbaum D. Close physical linkage of the FLT1 and FLT3 genes on chromosome 13 in man and chromosome 5 in mouse. Oncogene. 8:1993;173-179.
57. Spritz R. A., Strunk K. M., Lee S. T., Lu-Kuo J. M., Ward D. C., Le Paslier D., Altherr M. R., Dorman T. E., Moir D. T. A YAC contig spanning a cluster of human type III receptor protein tyrosine kinase genes (PDGFRA-KIT-KDR) in chromosome segment 4q12. Genomics. 22:1994;431-436.
58. Watkins-Chow D. E., Douglas K. R., Buckwalter M. S., Probst F. J., Camper S. A. Construction of a 3-Mb contig and partial transcript map of the central region of mouse chromosome 11. Genomics. 45:1997;147-157.
59. Kendall R. L., Thomas K. A. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc. Natl. Acad. Sci. USA. 90:1993;10705-10709.
60. Kendall R. L., Wang G., Thomas K. A. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem. Biophys. Res. Commun. 226:1996;324-328.
61. Pajusola K., Aprelikova O., Armstrong E., Morris S., Alitalo K. Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts. Oncogene. 8:1993;2931-2937.
62. Davis-Smyth T., Chen H., Park J., Presta L. G., Ferrara N. The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade. EMBO J. 15:1996;4919-4927.
63. Barleon B., Totzke F., Herzog C., Blanke S., Kremmer E., Siemeister G., Marme D., Martiny-Baron G. Mapping of the sites for ligand binding and receptor dimerization at the extracellular domain of the vascular endothelial growth factor receptor FLT-1. J. Biol. Chem. 272:1997;10382-10388.
64. Cunningham S. A., Stephan C. C., Arrate M. P., Ayer K. G., Brock T. A. Identification of the extracellular domains of Flt-1 that mediate ligand interactions. Biochem. Biophys. Res. Commun. 231:1997;596-599.
65. Fuh G., Li B., Crowley C., Cunningham B., Wells J. A. Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor. J. Biol. Chem. 273:1998;11197-11204.
66. Christinger H. W., Muller Y. A., Berleau L. T., Keyt B. A., Cunningham B. C., Ferrara N., de Vos A. M. Crystallization of the receptor binding domain of vascular endothelial growth factor. Proteins. 26:1996;353-357.
67. Wiesmann C., Fuh G., Christinger H. W., Eigenbrot C., Wells J. A., de Vos A. M. Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell. 91:1997;695-704.
68. Muller Y. A., Li B., Christinger H. W., Wells J. A., Cunningham B. C., de Vos A. M. Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site. Proc. Natl. Acad. Sci. USA. 94:1997;7192-7197.
69. Keyt B. A., Nguyen H. V., Berleau L. T., Duarte C. M., Park J., Chen H., Ferrara N. Identification of vascular endothelial growth factor determinants for binding KDR and FLT-1 receptors. Generation of receptor-selective VEGF variants by site-directed mutagenesis. J. Biol. Chem. 271:1996;5638-5646.
70. Stacker S. A., Stenvers K., Caesar C., Vitali A., Domagala T., Nice E., Roufail S., Sipmson R. J., Moritz R., Karpanen T., Alitalo K., Achen M. G. Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers. J. Biol. Chem. 1999.
71. Joukov V., Kumar V., Sorsa T., Arighi E., Weich H., Saksela O., Alitalo K. A recombinant mutant vascular endothelial growth factor-C that has lost vascular endothelial growth factor receptor-2 binding, activation, and vascular permeability activities. J. Biol. Chem. 273:1998;6599-6602.
72. Kaipainen A., Korhonen J., Pajusola K., Aprelikova O., Persico M. G., Terman B. I., Alitalo K. The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells. J. Exp. Med. 178:1993;2077-2088.
73. Partanen T. A., Makinen T., Arola J., Suda T., Weich H. A., Alitalo K. Endothelial growth factor receptors in human fetal heart. Circulation. 100:1999;583-586.
74. Barleon B., Sozzani S., Zhou D., Weich H. A., Mantovani A., Marme D. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood. 87:1996;3336-3343.
75. Clauss M., Weich H., Breier G., Knies U., Rockl W., Waltenberger J., Risau W. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J. Biol. Chem. 271:1996;17629-17634.
76. Charnock-Jones D. S., Sharkey A. M., Boocock C. A., Ahmed A., Plevin R., Ferrara N., Smith S. K. Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells. Biol. Reprod. 51:1994;524-530.
77. Takahashi T., Shirasawa T., Miyake K., Yahagi Y., Maruyama N., Kasahara N., Kawamura T., Matsumura O., Mitarai T., Sakai O. Protein tyrosine kinases expressed in glomeruli and cultured glomerular cells: Flt-1 and VEGF expression in renal mesangial cells. Biochem. Biophys. Res. Commun. 209:1995;218-226.
78. Katoh O., Tauchi H., Kawaishi K., Kimura A., Satow Y. Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation. Cancer Res. 55:1995;5687-5692.
79. Ziegler B. L., Valtieri M., Almeida Porada G., De Maria R., Muller R., Masella B., Gabbianelli M., Casella I., Pelosi E., Bock T., Zanjani E. D., Peschle C. KDR receptor: A key marker defining hematopoietic stem cells. Science. 285:1999;1553-1558.
80. Yang K., Cepko C. L. Flk-1, a receptor for vascular endothelial growth factor (VEGF), is expressed by retinal progenitor cells. J. Neurosci. 16:1996;6089-6099.
81. Kaipainen A., Korhonen J., Mustonen T., van Hinsbergh V. W., Fang G. H., Dumont D., Breitman M., Alitalo K. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc. Natl. Acad. Sci. USA. 92:1995;3566-3570.
82. Kukk E., Lymboussaki A., Taira S., Kaipainen A., Jeltsch M., Joukov V., Alitalo K. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development. 122:1996;3829-3837.
83. Valtola R., Salven P., Heikkila P., Taipale J., Joensuu H., Rehn M., Pihlajaniemi T., Weich H., deWaal R., Alitalo K. VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am. J. Pathol. 154:1999;1381-1390.
84. Jussila L., Valtola R., Partanen T. A., Salven P., Heikkila P., Matikainen M. T., Renkonen R., Kaipainen A., Detmar M., Tschachler E., Alitalo R., Alitalo K. Lymphatic endothelium and Kaposi's sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res. 58:1998;1599-1604.
85. Lymboussaki A., Partanen T. A., Olofsson B., Thomas-Crusells J., Fletcher C. D., de Waal R. M., Kaipainen A., Alitalo K. Expression of the vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors. Am. J. Pathol. 153:1998;395-403.
86. Hatva E., Kaipainen A., Mentula P., Jaaskelainen J., Paetau A., Haltia M., Alitalo K. Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. Am. J. Pathol. 146:1995;368-378.
87. Hatva E., Bohling T., Jaaskelainen J., Persico M. G., Haltia M., Alitalo K. Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas. Am. J. Pathol. 148:1996;763-775.
88. Marti H. H., Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc. Natl. Acad. Sci. USA. 95:1998;15809-15814.
89. Tuder R. M., Flook B. E., Voelkel N. F. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J. Clin. Invest. 95:1995;1798-1807.
90. Li J., Brown L. F., Hibberd M. G., Grossman J. D., Morgan J. P., Simons M. VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis. Am. J. Physiol. 270:1996;H1803-H1811.
91. Gerber H. P., Condorelli F., Park J., Ferrara N. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J. Biol. Chem. 272:1997;23659-23667.
92. Kappel A., Ronicke V., Damert A., Flamme I., Risau W., Breier G. Identification of vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) promoter/enhancer sequences sufficient for angioblast and endothelial cell-specific transcription in transgenic mice. Blood. 93:1999;4284-4292.
93. Wakiya K., Begue A., Stehelin D., Shibuya M. A cAMP response element and an Ets motif are involved in the transcriptional regulation of flt-1 tyrosine kinase (vascular endothelial growth factor receptor 1) gene. J. Biol. Chem. 271:1996;30823-30828.
94. Schorpp-Kistner M., Wang Z. Q., Angel P., Wagner E. F. JunB is essential for mammalian placentation. EMBO J. 18:1999;934-948.
95. Gerber H. P., McMurtrey A., Kowalski J., Yan M., Keyt B. A., Dixit V., Ferrara N. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J. Biol. Chem. 273:1998;30336-30343.
96. Waltenberger J., Claesson-Welsh L., Siegbahn A., Shibuya M., Heldin C. H. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J. Biol. Chem. 269:1994;26988-26995.
97. Seetharam L., Gotoh N., Maru Y., Neufeld G., Yamaguchi S., Shibuya M. A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene. 10:1995;135-147.
98. Kroll J., Waltenberger J. The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells. J. Biol. Chem. 272:1997;32521-32527.
99. Landgren E., Schiller P., Cao Y., Claesson-Welsh L. Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-gamma and migration of endothelial cells expressing Flt 1. Oncogene. 16:1998;359-367.
100. Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L. Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules. J. Biol. Chem. 273:1998;23410-23418.
101. Cunningham S. A., Waxham M. N., Arrate P. M., Brock T. A. Interaction of the Flt-1 tyrosine kinase receptor with the p85 subunit of phosphatidylinositol 3-kinase. Mapping of a novel site involved in binding. J. Biol. Chem. 270:1995;20254-20257.
102. Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I. Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2. Biochem. Biophys. Res. Commun. 246:1998;95-99.
103. 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. 95:1998;9349-9354.
104. Shen H., Clauss M., Ryan J., Schmidt A. M., Tijburg P., Borden L., Connolly D., Stern D., Kao J. Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. Blood. 81:1993;2767-2773.
105. Clauss M., Gerlach M., Gerlach H., Brett J., Wang F., Familletti P. C., Pan Y. C., Olander J. V., Connolly D. T., Stern D. Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J. Exp. Med. 172:1990;1535-1545.
106. Spyridopoulos I., Brogi E., Kearney M., Sullivan A. B., Cetrulo C., Isner J. M., Losordo D. W. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: Balance between growth and death signals. J. Mol. Cell. Cardiol. 29:1997;1321-1330.
107. Takahashi T., Shibuya M. The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-gamma pathway and partially induces mitotic signals in NIH3T3 fibroblasts. Oncogene. 14:1997;2079-2089.
108. Dougher-Vermazen M., Hulmes J. D., Bohlen P., Terman B. I. Biological activity and phosphorylation sites of the bacterially expressed cytosolic domain of the KDR VEGF-receptor. Biochem. Biophys. Res. Commun. 205:1994;728-738.
109. Igarashi K., Shigeta K., Isohara T., Yamano T., Uno I. Sck interacts with KDR and Flt-1 via its SH2 domain. Biochem. Biophys. Res. Commun. 251:1998;77-82.
110. D'Angelo G., Struman I., Martial J., Weiner R. I. Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin. Proc. Natl. Acad. Sci. USA. 92:1995;6374-6378.
111. Rousseau S., Houle F., Landry J., Huot J. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene. 15:1997;2169-2177.
112. Takahashi T., Ueno H., Shibuya M. VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene. 18:1999;2221-2230.
113. Satoh T., Fantl W. J., Escobedo J. A., Williams L. T., Kaziro Y. Platelet-derived growth factor receptor mediates activation of ras through different signaling pathways in different cell types. Mol. Cell. Biol. 13:1993;3706-3713.
114. Klint P., Kanda S., Kloog Y., Claesson-Welsh L. Contribution of Src and Ras pathways in FGF-2 induced endothelial cell differentiation. Oncogene. 18:1999;3354-3364.
115. Guo D., Jia Q., Song H. Y., Warren R. S., Donner D. B. Vascular endothelial cell growth factor promotes tyrosine phosphorylation of mediators of signal transduction that contain SH2 domains. Association with endothelial cell proliferation. J. Biol. Chem. 270:1995;6729-6733.
116. Xia P., Aiello L. P., Ishii H., Jiang Z. Y., Park D. J., Robinson G. S., Takagi H., Newsome W. P., Jirousek M. R., King G. L. Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J. Clin. Invest. 98:1996;2018-2026.
117. Criscuolo G. R., Lelkes P. I., Rotrosen D., Oldfield E. H. Cytosolic calcium changes in endothelial cells induced by a protein product of human gliomas containing vascular permeability factor activity. J. Neurosurg. 71:1989;884-891.
118. 2+ and von Willebrand factor release in human endothelial cells. Am. J. Pathol. 138:1991;213-221.
119. Parenti A., Morbidelli L., Cui X. L., Douglas J. G., Hood J. D., Granger H. J., Ledda F., Ziche M. Nitric oxide is an upstream signal of vascular endothelial growth factor-induced extracellular signal-regulated kinase1/2 activation in postcapillary endothelium. J. Biol. Chem. 273:1998;4220-4226.
120. Fulton D., Gratton J. P., McCabe T. J., Fontana J., Fujio Y., Walsh K., Franke T. F., Papapetropoulos A., Sessa W. C. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 399:1999;597-601.
121. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., Zeiher A. M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 399:1999;601-605.
122. Clapp C., Martial J. A., Guzman R. C., Rentier-Delure F., Weiner R. I. The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology. 133:1993;1292-1299.
123. Struman I., Bentzien F., Lee H., Mainfroid V., D'Angelo G., Goffin V., Weiner R. I., Martial J. A. Opposing actions of intact and N-terminal fragments of the human prolactin/growth hormone family members on angiogenesis: An efficient mechanism for the regulation of angiogenesis. Proc. Natl. Acad. Sci. USA. 96:1999;1246-1251.
124. Carmeliet P., Lampugnani M. G., Moons L., Breviario F., Compernolle V., Bono F., Balconi G., Spagnuolo R., Oostuyse B., Dewerchin M., Zanetti A., Angellilo A., Mattot V., Nuyens D., Lutgens E., Clotman F., de Ruiter M. C., Gittenberger-de Groot A., Poelmann R., Lupu F., Herbert J. M., Collen D., Dejana E. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell. 98:1999;147-157.
125. Brooks P. C., Montgomery A. M., Rosenfeld M., Reisfeld R. A., Hu T., Klier G., Cheresh D. A. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 79:1994;1157-1164.
126. Stromblad S., Becker J. C., Yebra M., Brooks P. C., Cheresh D. A. Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin alphaVbeta3 during angiogenesis. J. Clin. Invest. 98:1996;426-433.
127. Scatena M., Almeida M., Chaisson M. L., Fausto N., Nicosia R. F., Giachelli C. M. NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival. J. Cell Biol. 141:1998;1083-1093.
128. Soldi R., Mitola S., Strasly M., Defilippi P., Tarone G., Bussolino F. Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. EMBO J. 18:1999;882-892.
129. Abedi H., Zachary I. Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. J. Biol. Chem. 272:1997;15442-15451.
130. Liu Z. Y., Ganju R. K., Wang J. F., Schweitzer K., Weksler B., Avraham S., Groopman J. E. Characterization of signal transduction pathways in human bone marrow endothelial cells. Blood. 90:1997;2253-2259.
131. Pepper M. S., Ferrara N., Orci L., Montesano R. Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochem. Biophys. Res. Commun. 181:1991;902-906.
132. Unemori E. N., Ferrara N., Bauer E. A., Amento E. P. Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J. Cell Physiol. 153:1992;557-562.
133. Lamoreaux W. J., Fitzgerald M. E., Reiner A., Hasty K. A., Charles S. T. Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvasc. Res. 55:1998;29-42.
134. Zucker S., Mirza H., Conner C. E., Lorenz A. F., Drews M. H., Bahou W. F., Jesty J. Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: Conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int. J. Cancer. 75:1998;780-786.
135. Senger D. R., Claffey K. P., Benes J. E., Perruzzi C. A., Sergiou A. P., Detmar M. Angiogenesis promoted by vascular endothelial growth factor: Regulation through alpha1beta1 and alpha2beta1 integrins. Proc. Natl. Acad. Sci. USA. 94:1997;13612-13617.
136. Gerber H. P., Dixit V., Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J. Biol. Chem. 273:1998;13313-13316.
137. Mechtcheriakova D., Wlachos A., Holzmuller H., Binder B. R., Hofer E. Vascular endothelial cell growth factor-induced tissue factor expression in endothelial cells is mediated by EGR-1. Blood. 93:1999;3811-3823.
138. Armesilla A. L., Lorenzo E., Gomez del Arco P., Martinez-Martinez S., Alfranca A., Redondo J. M. Vascular endothelial growth factor activates nuclear factor of activated T cells in human endothelial cells: A role for tissue factor gene expression. Mol. Cell. Biol. 19:1999;2032-2043.
139. Korpelainen E. I., Karkkainen M., Gunji Y., Vikkula M., Alitalo K. Endothelial receptor tyrosine kinases activate the STAT signaling pathway: Mutant Tie-2 causing venous malformations signals a distinct STAT activation response. Oncogene. 18:1999;1-8.
140. Fournier E., Dubreuil P., Birnbaum D., Borg J. P. Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor. Oncogene. 11:1995;921-931.
141. Pajusola K., Aprelikova O., Pelicci G., Weich H., Claesson-Welsh L., Alitalo K. Signaling properties of FLT4, a proteolytically processed receptor tyrosine kinase related to two VEGF receptors. Oncogene. 9:1994;3545-3555.
142. Fournier E., Rosnet O., Marchetto S., Turck C. W., Rottapel R., Pelicci P. G., Birnbaum D., Borg J. P. Interaction with the phosphotyrosine binding domain/phosphotyrosine interacting domain of SHC is required for the transforming activity of the FLT4/VEGFR3 receptor tyrosine kinase. J. Biol. Chem. 271:1996;12956-12963.
143. Cao Y., Linden P., Farnebo J., Cao R., Eriksson A., Kumar V., Qi J. H., Claesson-Welsh L., Alitalo K. Vascular endothelial growth factor C induces angiogenesis in vivo. Proc. Natl. Acad. Sci. USA. 95:1998;14389-14394.
144. Fournier E., Blaikie P., Rosnet O., Margolis B., Birnbaum D., Borg J. P. Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF receptor 3 signaling. Oncogene. 18:1999;507-514.
145. Wang J. F., Ganju R. K., Liu Z. Y., Avraham H., Avraham S., Groopman J. E. Signal transduction in human hematopoietic cells by vascular endothelial growth factor related protein, a novel ligand for the FLT4 receptor. Blood. 90:1997;3507-3515.
146. Ferrell R. E., Levinson K. L., Esman J. H., Kimak M. A., Lawrence E. C., Barmada M. M., Finegold D. N. Hereditary lymphedema: Evidence for linkage and genetic heterogeneity. Hum. Mol. Genet. 7:1998;2073-2078.
147. Shalaby F., Rossant J., Yamaguchi T. P., Gertsenstein M., Wu X. F., Breitman M. L., Schuh A. C. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 376:1995;62-66.
148. Fong G. H., Rossant J., Gertsenstein M., Breitman M. L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 376:1995;66-70.
149. Fong G. H., Zhang L., Bryce D. M., Peng J. Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development. 126:1999;3015-3025.
150. Dumont D. J., Jussila L., Taipale J., Lymboussaki A., Mustonen T., Pajusola K., Breitman M., Alitalo K. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science. 282:1998;946-949.
151. Jeltsch M., Kaipainen A., Joukov V., Meng X., Lakso M., Rauvala H., Swartz M., Fukumura D., Jain R. K., Alitalo K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 276:1997;1423-1425.
152. Larcher F., Murillas R., Bolontrade M., Conti C. J., Jorcano J. L. VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development. Oncogene. 17:1998;303-311.
153. Detmar M., Brown L. F., Schon M. P., Elicker B. M., Velasco P., Richard L., Fukumura D., Monsky W., Claffey K. P., Jain R. K. Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J. Invest. Dermatol. 111:1998;1-6.
154. 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. 7:1991;295-307.
155. Takagi S., Kasuya Y., Shimizu M., Matsuura T., Tsuboi M., Kawakami A., Fujisawa H. Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. Dev. Biol. 170:1995;207-222.
156. Kawakami A., Kitsukawa T., Takagi S., Fujisawa H. Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. J. Neurobiol. 29:1996;1-17.
157. Fujisawa H., Kitsukawa T., Kawakami A., Takagi S., Shimizu M., Hirata T. Roles of a neuronal cell-surface molecule, neuropilin, in nerve fiber fasciculation and guidance. Cell Tissue Res. 290:1997;465-470.
158. Kitsukawa T., Shimono A., Kawakami A., Kondoh H., Fujisawa H. Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development. 121:1995;4309-4318.
159. Kitsukawa T., Shimizu M., Sanbo M., Hirata T., Taniguchi M., Bekku Y., Yagi T., Fujisawa H. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron. 19:1997;995-1005.
160. Miao H.-Q., Soker S., Feiner L., Alonso J. L., Raper J. A., Klagsbrun M. 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. 146:1999;233-241.
161. Feiner L., Koppel A. M., Kobayashi H., Raper J. A. Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ. Neuron. 19:1997;539-545.
162. Nakamura F., Tanaka M., Takahashi T., Kalb R. G., Strittmatter S. M. Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron. 21:1998;1093-1100.
163. Chen H., Chedotal A., He Z., Goodman C. S., Tessier-Lavigne M. 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. 19:1997;547-559.
164. Sondell M., Lundborg G., Kanje M. Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J. Neurosci. 19:1999;5731-5740.
165. Gale N. W., Yancopoulos G. D. Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. 13:1999;1055-1066.
166. Oh H., Takagi H., Suzuma K., Otani A., Matsumura M., Honda Y. Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J. Biol. Chem. 274:1999;15732-15739.
167. Bouloumie A., Schini-Kerth V. B., Busse R. Vascular endothelial growth factor up-regulates nitric oxide synthase expression in endothelial cells. Cardiovasc. Res. 41:1999;773-780.
168. Kroll J., Waltenberger J. VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR). Biochem. Biophys. Res. Commun. 252:1998;743-746.
169. Hood J. D., Meininger C. J., Ziche M., Granger H. J. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am. J. Physiol. 274:1998;H1054-H1058.
170. Chen Z., Fisher R. J., Riggs C. W., Rhim J. S., Lautenberger J. A. Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides. Cancer Res. 57:1997;2013-2019.
171. Arkonac B. M., Foster L. C., Sibinga N. E., Patterson C., Lai K., Tsai J. C., Lee M. E., Perrella M. A., Haber E. Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like growth factor in vascular endothelial cells. J. Biol. Chem. 273:1998;4400-4405.
172. Shen B. Q., Lee D. Y., Gerber H. P., Keyt B. A., Ferrara N., Zioncheck T. F. Homologous up-regulation of KDR/Flk-1 receptor expression by vascular endothelial growth factor in vitro. J. Biol. Chem. 273:1998;29979-29985.
173. Mandriota S. J., Seghezzi G., Vassalli J. D., Ferrara N., Wasi S., Mazzieri R., Mignatti P., Pepper M. S. Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. J. Biol. Chem. 270:1995;9709-9716.