Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt

Vaibhav Katkade; Abigail A. Soyombo; Irma Isordia-Salas; Harlan N. Bradford; John P. Gaughan; Robert W. Colman; Tracee S. Panetti

doi:10.1160/TH04-12-0834

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(03): 606-614
DOI: 10.1160/TH04-12-0834

Endothelium and Vascular Development

Schattauer GmbH

Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt

Vaibhav Katkade

¹Sol Sherry Thrombosis Research Center

²Department of Microbiology and Immunology

,

Abigail A. Soyombo

¹Sol Sherry Thrombosis Research Center

,

Irma Isordia-Salas

¹Sol Sherry Thrombosis Research Center

,

Harlan N. Bradford

¹Sol Sherry Thrombosis Research Center

,

John P. Gaughan

³Department of Biostatistics, Temple University School of Medicine, Philadelphia, USA

,

Robert W. Colman

¹Sol Sherry Thrombosis Research Center

,

Tracee S. Panetti

¹Sol Sherry Thrombosis Research Center

²Department of Microbiology and Immunology

› Author Affiliations

Abstract

Summary

Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the PI3-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response to VEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3α.HKa and D5 inhibit phosphorylation of Akt and GSK-3α after stimulation withVEGF and S1P. Inhibitors of Akt and PI3-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters PI3-kinase- Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.

Keywords

Angiogenesis - high molecular weight kininogen - sphingosine 1-phosphate - vascular endothelial growth factor - migration

Full Text

References

References
1 Folkman J, Shing Y. Angiogenesis.. J Biol Chem 1992; 267: 10931-4.
2 Auerbach W, Auerbach R. Angiogenesis inhibition: A review.. Pharmac Ther 1994; 63: 265-311.
3 Folkman J. Endogenous angiogenesis inhibitors.. APMIS 2004; 112: 496-507.
4 Colman RW, Schmaier AH. Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes.. Blood 1997; 90: 3819-43.
5 Shariat-Madar Z, Mahdi F, Schmaier AH. Recombinant prolylcarboxypeptidase activates plasma prekallikrein.. Blood 2004; 103: 4554-61.
6 Guo YL, Wang S, Colman RW. Kininostatin, an angiogenic inhibitor, inhibits proliferation and induces apoptosis of human endothelial cells.. Arterioscler Thromb Vasc Biol 2001; 21: 1427-33.
7 Colman RW, Jameson BA, Lin Y. et al. Domain 5 of high molecular weight kininogen (kininostatin) downregulates endothelial cell proliferation and migration and inhibits angiogenesis.. Blood 2000; 95: 543-50.
8 Song JS, Sainz IM, Cosenza SC. et al. Inhibition of tumor angiogenesis in vivo by a monoclonal antibody targeted to domain 5 of high molecular weight kininogen.. Blood 2004; 104: 2065-72.
9 Cao DJ, Guo YL, Colman RW. Urokinase-type plasminogen activator receptor is involved in mediating the apoptotic effect of cleaved high molecular weight kininogen in human endothelial cells.. Circ Res 2004; 94: 1227-34.
10 Wang S, Hasham MG, Isordia-Salas I. et al. Upregulation of Cdc2 and cyclin A during apoptosis of endothelial cells induced by cleaved high-molecularweight kininogen.. Am J Physiol Heart Circ Physiol 2003; 284: H1917-H1923.
11 Colman RW, Pixley RA, Najamunnisa S. et al. Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor.. J Clin Invest 1997; 100: 1481-7.
12 Zhang JC, Donate F, Qi X. et al. The antiangiogenic activity of cleaved high molecular weight kininogen is mediated through binding to endothelial cell tropomyosin.. Proc Natl Acad Sci U S A 2002; 99: 12224-9.
13 Hasan AA, Zisman T, Schmaier AH. Identification of cytokeratin 1 as a binding protein and presentation receptor for kininogens on endothelial cells.. Proc Natl Acad Sci U S A 1998; 95: 3615-20.
14 Joseph K, Ghebrehiwet B, Kaplan AP. Cytokeratin 1 and gC1qR mediate high molecular weight kininogen binding to endothelial cells.. Clin Immunol 1999; 92: 246-55.
15 Mahdi F, Shariat-Madar Z, Todd RF. III et al. Expression and colocalization of cytokeratin 1 and urokinase plasminogen activator receptor on endothelial cells.. Blood 2001; 97: 2342-50.
16 Mahdi F, Shariat-Madar Z, Kuo A. et al. Mapping the interaction between high molecular mass kininogen and the urokinase plasminogen activator receptor.. J Biol Chem 2004; 279: 16621-8.
17 Panetti TS. Differential effects of sphingosine 1-phosphate and lysophosphatidic acid on endothelial cells.. Biochim Biophys Acta 2002; 1582: 190-6.
18 Neufeld G, Cohen T, Gengrinovitch S. et al. Vascular endothelial growth factor (VEGF) and its receptors.. FASEB J 1999; 13: 9-22.
19 Lee M-J, Thangada S, Claffey KP. et al. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate.. Cell 1999; 99: 301-12.
20 Kimura T, Watanabe T, Sato K. et al. Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3.. Biochem J 2000; 348 Pt 1 71-6.
21 Kono M, Mi Y, Liu Y. et al. The Sphingosine- 1-phosphate Receptors S1P1, S1P2, and S1P3 Function Coordinately during Embryonic Angiogenesis.. J Biol Chem 2004; 279: 29367-73.
22 Panetti TS, Nowlen JK, Mosher DF. Sphingosine- 1-phosphate and lysophosphatidic acid stimulate endothelial cell migration.. Arterioscler Thromb Vasc Biol 2000; 20: 1013-9.
23 Petrova TV, Makinen T, Alitalo K. Signaling via vascular endothelial growth factor receptors.. Exp Cell Res 1999; 253: 117-30.
24 Hla T. Sphingosine 1-phosphate receptors.. Prostaglandins Other Lipid Mediat 2001; 64: 135-42.
25 Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis.. Circ Res 2002; 90: 1243-50.
26 Rosig L, Badorff C, Holzmann Y. et al. Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1 degradation.. J Biol Chem 2002; 277: 9684-9.
27 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 1997; 272: 15442-51.
28 Panetti TS. Tyrosine phosphorylation of paxillin, FAK, and p130Cas: Effects on cell spreading and migration.. Front Biosci 2002; 7: D143-D150.
29 Guo YL, Wang S, Cao DJ. et al. Apoptotic effect of cleaved high molecular weight kininogen is regulated by extracellular matrix proteins.. J Cell Biochem 2003; 89: 622-32.
30 Kunapuli SP, De la Cadena RA, Colman RW. Deletion mutagenesis of high molecular weight kininogen light chain.. J Biol Chem 1993; 268: 2486-92.
31 Pace CN, Vajdos F, Fee L. et al. How to measure and predict the molar absorption coefficient of a protein.. Protein Sci 1995; 4: 2411-23.
32 Gum R, Juarez J, Allgayer H. et al. Stimulation of urokinase-type plasminogen activator receptor expression by PMA requires JNK1-dependent and -independent signaling modules.. Oncogene 1998; 17: 213-25.
33 Zhang JC, Claffey K, Sakthivel R. et al. Two-chain high molecular weight kininogen induces endothelial cell apoptosis and inhibits angiogenesis: partial activity within domain 5.. FASEB J 2000; 14: 2589-600.
34 Turner CE. Paxillin and focal adhesion signalling.. Nat Cell Biol 2000; 2: E231-E236.
35 Lee MJ, Thangada S, Paik JH. et al. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis.. Mol Cell 2001; 8: 693-704.
36 Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family.. Cardiovasc Res 2001; 49: 568-81.
37 Panetti TS, Hannah DF, Avraamides C. et al. Extracellular matrix molecules regulate endothelial cell migration stimulated by lysophosphatidic acid.. J Thromb Haemost 2004; 2: 1645-56.
38 Eriksson K, Magnusson P, Dixelius J. et al. Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways.. FEBS Lett 2003; 536: 19-24.
39 Wajih N, Sane DC. Angiostatin selectively inhibits signaling by hepatocyte growth factor in endothelial and smooth muscle cells.. Blood 2003; 101: 1857-63.
40 Sudhakar A, Sugimoto H, Yang C. et al. Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins.. Proc Natl Acad Sci U S A 2003; 100: 4766-71.
41 Argraves KM, Wilkerson BA, Argraves WS. et al. Sphingosine-1-phosphate signaling promotes critical migratory events in vasculogenesis.. J Biol Chem 2004; 279: 50580-90.
42 Chae SS, Paik JH, Furneaux H, Hla T. Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference.. J Clin Invest 2004; 114: 1082-9.
43 Yatomi Y, Ohmori T, Rile G. et al. Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells.. Blood 2000; 96: 3431-8.
44 Panetti TS, Chen H, Misenheimer TM. et al. Endothelial cell mitogenesis induced by LPA: Inhibition by thrombospondins –1 and –2.. J Lab Clin Med 1997; 129: 208-16.
45 Short SM, Talbott GA, Juliano RL. Integrin-mediated signaling events in human endothelial cells.. Mol Biol Cell 1998; 9: 1969-80.
46 Goel HL, Dey CS. Insulin stimulates spreading of skeletal muscle cells involving the activation of focal adhesion kinase, phosphatidylinositol 3-kinase and extracellular signal regulated kinases.. J Cell Physiol 2002; 193: 187-98.
47 Fujio Y, Walsh K. Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner.. J Biol Chem 1999; 274: 16349-54.