Crotalid venom vascular endothelial growth factors has preferential affinity for VEGFR-1

Yuh-Ling Chen; Inn-Ho Tsai; Tse-Ming Hong; Shu-Huei Tsai

doi:10.1160/TH04-09-0568

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(02): 331-338
DOI: 10.1160/TH04-09-0568

Endothelium and Vascular Development

Schattauer GmbH

Crotalid venom vascular endothelial growth factors has preferential affinity for VEGFR-1

Characterization of Protobothrops mucrosquamatus venom VEGF

Authors

Yuh-Ling Chen

¹Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

²Institute of Oral Medicine, National Cheng Kung University, Tainan, Taiwan
Inn-Ho Tsai

¹Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
Tse-Ming Hong

³School of Pharmacy, National Taiwan University, Taipei, Taiwan
Shu-Huei Tsai

⁴Department of Orthopaedics and Traumatology, School of Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

Abstract

Summary

Pm-VEGF, a novel member ofVEGF family from the venom gland of Taiwan habu (Protobothrops mucrosquamatu), is a disulfidelinked homodimer with 119 amino acid residues. Recombinant fusion Pm-VEGF was expressed in Escherichia coli, purified and refolded. Surface plasmon resonance was used to determine its binding kinetics toVEGF-receptors (VEGFR). Relative to human VEGF₁₆₅, the binding affinity of Pm-VEGF to the VEGFR-1 was 1.7-fold higher while affinity to the VEGFR-2 was 17-fold lower. But it did not bind theVEGFR-3 or neuropilin-1. Pm-VEGF promoted the proliferation and tissue factor production of endothelial cells, the neovascularization in the chicken chorioallantoic membrane, and increased vascular permeability. It also stimulated tissue-factor production and human monocyte chemotaxis, in accord with its specificity for VEGFR-1. Structural comparison among VEGF-proteins from various viper venoms revealed that the two subfamilies of vipers (Crotalinae and Viperinae) have evolved with distinct receptor-specificities for VEGFR-1 and VEGFR-2, respectively. Discussion on structureactivity relationships of the VEGFs further provided insight into residues important for the receptor-binding and specificities.

Keywords

Snake venom VEGF - receptor specificity - vascular permeability - angiogenesis - monocyte chemotaxis

Full Text

References

References
1 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor.. Endocr Rev 1997; 18: 4-25.
2 Ferrara N, Gerber H-P, LeCouter J. The biology of VEGF and its receptors.. Nat Med 2003; 9: 669-76.
3 Ferrara N. Molecular and biological properties of vascular endothelial growth factor.. J Mol Med 1999; 77: 527-43.
4 Clauss M, Gerlach M, Gerlach H. et al Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.. J Exp Med 1990; 172: 1535-45.
5 Broxmeyer HE, Cooper S, Li ZH. et al Myeloid progenitor cell regulatory effects of vascular endothelial cell growth factor.. Int J Hematol 1995; 62: 203-15.
6 Gerber HP, Malik AK, Solar GP. et al VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism.. Nature 2002; 417: 954-8.
7 de Vries C, Escobedo JA, Ueno H. et al The fmslike tyrosine kinase, a receptor for vascular endothelial growth factor.. Science 1992; 255: 989-91.
8 Terman I B, 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: 1579-86.
9 Barleon B, Sozzani S, Zhou D. et al Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1.. Blood 1996; 87: 3336-43.
10 Shibuya M. Structure and function of VEGF/ VEGF-receptor system involved in angiogenesis.. Cell Struct Funct 2001; 26: 25-35.
11 Shalaby F, Rossant J, Yamaguchi TP. et al Failure of blood-island formation and vasculogenesis in Flk- 1-deficient mice.. Nature 1995; 376: 62-6.
12 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.
13 Clauss M. Molecular biology of the VEGF and the VEGF receptor family.. Semin Thromb Hemost 2000; 26: 561-9.
14 Park JE, Chen HH, Winer J. et al Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR.. J Biol Chem 1994; 269: 25646-54.
15 Neufeld G, Cohen T, Gengrinovitch S. et al Vascular endothelial growth factor (VEGF) and its receptors.. FASEB J 1999; 13: 9-22.
16 Luttun A, Tjwa M, Moons L. et al Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1.. Nat Med 2002; 8: 831-40.
17 Hattori K, Heissig B, Wu Y. et al Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment.. Nat Med 2002; 8: 841-9.
18 Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors.. J Cell Sci 2001; 114: 853-65.
19 Lange T, Guttmann-Raviv N, Baruch L. et al VEGF162, a new heparin-binding vascular endothelial growth factor splice form that is expressed in transformed human cells.. J Biol Chem 2003; 278: 17164-9.
20 Houck KA, Leung DW, Rowland AM. et al Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms.. J Biol Chem 1992; 267: 26031-7.
21 Olofsson B, Pajusola K, von Euler G. et al 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 1996; 271: 19310-7.
22 Joukov V, Pajusola K, Kaipainen A. et al 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 1996; 15: 290-8.
23 Li X, Eriksson U. Novel VEGF family members: VEGF-B, VEGF-C and VEGF-D.. Int J Biochem Cell Biol 2001; 33: 421-6.
24 Meyer M, Clauss M, Lepple-Wienhues A. et al A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases.. EMBO J 1999; 18: 363-74.
25 Komori Y, Sugihara H. (1990) Purification and physiological study of a hypotensive factor from the venom of Vipera aspis aspis (aspic viper).. Toxicon 1990; 28: 359-69.
26 Komori Y, Nikai T, Taniguchi K. et al Vascular endothelial growth factor VEGF-like heparin-binding protein from the venom of Vipera aspis aspis (Aspic viper).. Biochemistry 1999; 38: 11769-8.
27 Gasmi A, Abidi F, Srairi N. et al Purification and characterization of a growth factor-like which increases capillary permeability from Vipera lebetina venom.. Biochem Biophys Res Commun 2000; 268: 69-72.
28 Gasmi A, Bourcier C, Aloui Z. et al (2002) Complete structure of an increasing capillary permeability protein (ICPP) purified from Vipera lebetina venom. ICPP is angiogenic via vascular endothelial growth factor receptor signalling.. J Biol Chem 2002; 277: 29992-8.
29 Junqueira de Azevedo IL, Farsky SH. et al Molecular cloning and expression of a functional snake venom vascular endothelium growth factor (VEGF) from the Bothrops insularis pit viper. A new member of the VEGF family of proteins.. J Biol Chem 2001; 276: 39836-42.
30 Tsai IH, Lu PJ, Wang YM. et al Molecular cloning and characterization of a neurotoxic phospholipase A 2 from the venom of Taiwan habu (Trimeresurus mucrosquamatus).. Biochem J 1995; 311: 895-900.
31 Sozzani SW, Luini W, Molino M. et al The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine.. J Immunol 1991; 147: 2215-21.
32 McDonald NQ, Hendrickson WA. A structural superfamily of growth factors containing a cystine knot motif.. Cell 1993; 73: 421-4.
33 Waltenberger J, Claesson-Welsh L, Siegbahn A. et al Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor.. J Biol Chem 1994; 269: 26988-95.
34 Miles AA, Wilhelm DL. Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. I. An activable permeability factor and its inhibitor in guinea-pig serum.. Br J Exp Pathol 1955; 36: 71-81.
35 Schratzberger P, Kahler CM, Wiedermann CJ. (1996) Use of fluorochromes in the determination of chemotaxis and haptotaxis of granulocytes by micropore filter assays.. Ann Hematol 1996; 72: 23-7.
36 Takahashi H, Hattori S, Iwamatsu A. et al A novel snake venom vascular endothelial growth factor (VEGF) predominantly induces vascular permeability through preferential signaling via VEGF receptor-1.. J Biol Chem 2004; 279: 46304-14.
37 Scrofani SD, Fabri LJ, Xu P. et al Purification and refolding of vascular endothelial growth factor-B.. Protein Sci 2000; 9: 2018-25.
38 Siemeister G, Schnurr B, Mohrs K. et al Expression of biologically active isoforms of the tumor angiogenesis factor VEGF in Escherichia coli.. BBRC 1996; 222: 249-55.
39 Hung CC, Chiou SH.. Fibrinogenolytic proteases isolated from the snake venom of Taiwan habu: serine proteases with kallikrein-like and angiotensin-degrading activities. Biochem. Biophys Res Commun 2001; 281: 1012-8.
40 Liu CS, Chen JM, Chang CH. et al The amino acid sequence and properties of an edema-inducing Lys-49 phospholipase A 2 homolog from the venom of Trimeresurus mucrosquamatus.. Biochim Biophys Acta, 1991; 1077: 362-70.
41 Yamazaki Y, Takani K, Atoda H. et al Snake venom vascular endothelial growth factors (VEGFs) exhibit potent activity through their specific recognition of KDR (VEGF receptor 2).. J Biol Chem 2003; 278: 51985-8.
42 Wiesmann C, Fuh G, Christinger HW. et al Crystal structure at 1.7 Å resolution of VEGF in complex with domain 2 of the Flt-1 receptor.. Cell 1997; 91: 695-704.
43 Muller YA, Li B, Christinger HW. et al Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site.. Proc Natl Acad Sci USA 1997; 94: 7192-7.
44 Li B, Fuh G, Meng G. et al Receptor-selective variants of human vascular endothelial growth factor: generation and characterization.. J Biol Chem 2000; 275: 29823-8.
45 Higgins D, Thompson J, Gibson T. et al CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position- specific gap penalties and weight matrix choice.. Nucleic Acids Res 1994; 22: 4673-80.