Interaction of high-molecular-weight kininogen with endothelial cell binding proteins suPAR, gC1qR and cytokeratin 1 determined by Surface Plasmon Resonance (BiaCore)

Robin A. Pixley; Ricardo G. Espinola; Berhane Ghebrehiwet; Kusumam Joseph; Alice Kao; Khalil Bdeir; Douglas B. Cines; Robert W. Colman

doi:10.1160/TH10-09-0591

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(06): 1053-1059
DOI: 10.1160/TH10-09-0591

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Interaction of high-molecular-weight kininogen with endothelial cell binding proteins suPAR, gC1qR and cytokeratin 1 determined by Surface Plasmon Resonance (BiaCore)

Authors

Robin A. Pixley^*

¹The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Ricardo G. Espinola^*

¹The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Berhane Ghebrehiwet

²Department of Medicine, Stony Brook University, Stony Brook, New York, USA
Kusumam Joseph

³Medical University of South Carolina, Charleston, South Carolina, USA
Alice Kao

⁴University of Pennsylvania, Philadelphia, Pennsylvania, USA
Khalil Bdeir

⁴University of Pennsylvania, Philadelphia, Pennsylvania, USA
Douglas B. Cines

⁴University of Pennsylvania, Philadelphia, Pennsylvania, USA
Robert W. Colman

¹The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

Abstract

Summary

The physiologic activation of the plasma kallikrein-kinin system requires the assembly of its constituents on a cell membrane. High-molecular-weight kininogen (HK) and cleaved HK (HKa) both interact with at least three endothelial cell binding proteins: urokinase plasminogen activator receptor (uPAR), globular C1q receptor (gC1qR,) and cytokeratin 1 (CK1). The affinity of HK and HKa for endothelial cells are KD=7–52 nM. The contribution of each protein is unknown. We examined the direct binding of HK and HKa to the soluble extracellular form of uPAR (suPAR), gC1qR and CK1 using surface plasmon resonance. Each binding protein linked to a CM-5 chip and the association, dissociation and KD (equilibrium constant) were measured. The interaction of HK and HKa with each binding protein was zinc-dependent. The affinity for HK and HKa was gC1qR>CK1>suPAR, indicating that gC1qR is dominant for binding. The affinity for HKa compared to HK was the same for gC1qR, 2.6-fold tighter for CK1 but 53-fold tighter for suPAR. Complex between binding proteins was only observed between gC1qR and CK1 indicating that a binary CK1-gC1qR complex can form independently of kininogen. Although suPAR has the weakest affinity of the three binding proteins, it is the only one that distinguished between HK and HKa. This finding indicates that uPAR may be a key membrane binding protein for differential binding and signalling between the cleaved and uncleaved forms of kininogen. The role of CK1 and gC1qR may be to initially bind HK to the membrane surface before productive cleavage to HKa.

Keywords

Kininogen - surface plasmon resonance - suPAR - gC1qR - cytokeratin 1

Full Text

References

References
1 Scott CF, Shull B, Muller-Esterl W. et al. Rapid direct determination of low and high molecular weight kininogen in human plasma by Particle Concentration Fluorescence Immunoassay (PCFIA). Thromb Haemost 1997; 77: 109-118.
2 Bradford HN, Dela Cadena RA, Kunapuli SP. et al. Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex. Blood 1997; 90: 1508-1515.
3 Hassan S, Sainz IM, Khan MM. et al. Antithrombotic activity of kininogen is mediated by inhibitory effects of domain 3 during arterial injury in vivo. Am J Physiol Heart Circ Physiol 2007; 292: H2959-2965.
4 Bradford HN, Jameson BA, Adam AA. et al. Contiguous binding and inhibitory sites on kininogens required for the inhibition of platelet calpain. J Biol Chem 1993; 268: 26546-26551.
5 Yung LY, Lim F, Khan MM. et al. Neutrophil adhesion on surfaces preadsorbed with high molecular weight kininogen under well-defined flow conditions. Immunopharmacology 1996; 32: 19-23.
6 Lin Y, Harris RB, Yan W. et al. High molecular weight kininogen peptides inhibit the formation of kallikrein on endothelial cell surfaces and subsequent urokinase-dependent plasmin formation. Blood 1997; 90: 690-697.
7 Jacobsen S, Kriz M. Some data on two purified kininogens from human plasma. Br J Pharmacol Chemother 1967; 29: 25-36.
8 Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524-526.
9 Schapira M, Scott CF, Colman RW. Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest 1982; 69: 462-468.
10 Silverberg M, Longo J, Kaplan AP. Study of the effect of high molecular weight kininogen upon the fluid-phase inactivation of kallikrein by C1 inhibitor. J Biol Chem 1986; 261: 14965-14968.
11 Villanueva GB, Leung L, Bradford H. et al. Conformation of high molecular weight kininogen: effects of kallikrein and factor XIa cleavage. Biochem Biophys Res Commun 1989; 158: 72-79.
12 Weisel JW, Nagaswami C, Woodhead JL. et al. The shape of high molecular weight kininogen. Organization into structural domains, changes with activation, and interactions with prekallikrein, as determined by electron microscopy. J Biol Chem 1994; 269: 10100-10106.
13 Khan MM, Bradford HN, Isordia-Salas I. et al. High-molecular-weight kininogen fragments stimulate the secretion of cytokines and chemokines through uPAR, Mac-1, and gC1qR in monocytes. Arterioscler Thromb Vasc Biol 2006; 26: 2260-2266.
14 Keith Jr. JC, Sainz IM, Isordia-Salas I. et al. A monoclonal antibody against kininogen reduces inflammation in the HLA-B27 transgenic rat. Arthritis Res Ther 2005; 7: R769-776.
15 Espinola RG, Uknis A, Sainz IM. et al. A monoclonal antibody to high-molecular weight kininogen is therapeutic in a rodent model of reactive arthritis. Am J Pathol 2004; 165: 969-976.
16 Colman RW. The contact system: a pro-inflammatory pathway with antithrombotic activity. Nat Med 1998; 4: 277-278.
17 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: 1427-1433.
18 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: 1227-1234.
19 Colman RW, Jameson BA, Lin Y. et al. Domain 5 of high molecular weight kininogen (kininostatin) down-regulates endothelial cell proliferation and migration and inhibits angiogenesis. Blood 2000; 95: 543-550.
20 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: 1481-1487.
21 Joseph K, Ghebrehiwet B, Peerschke EI. et al. Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular “heads” of C1q (gC1q-R). Proc Natl Acad Sci USA 1996; 93: 8552-8557.
22 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 USA 1998; 95: 3615-3620.
23 Joseph K, Ghebrehiwet B, Kaplan AP. Cytokeratin 1 and gC1qR mediate high molecular weight kininogen binding to endothelial cells. Clin Immunol 1999; 92: 246-255.
24 Joseph K, Tholanikunnel BG, Ghebrehiwet B. et al. Interaction of high molecular weight kininogen binding proteins on endothelial cells. Thromb Haemost 2004; 91: 61-70.
25 Chavakis T, Kanse SM, Pixley RA. et al. Regulation of leukocyte recruitment by polypeptides derived from high molecular weight kininogen. Faseb J 2001; 15: 2365-2376.
26 Bdeir K, Kuo A, Sachais BS. et al. The kringle stabilizes urokinase binding to the urokinase receptor. Blood 2003; 102: 3600-3608.
27 Ghebrehiwet B, Peerschke EI. Structure and function of gC1q-R: a multiligand binding cellular protein. Immunobiology 1998; 199: 225-238.
28 Colman RW, Wu Y, Liu Y. Mechanisms by which cleaved kininogen inhibits endothelial cell differentiation and signalling. Thromb Haemost 2010; 104: 875-885.
29 Ploug M, Ronne E, Behrendt N. et al. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosylphosphatidylinositol. J Biol Chem 1991; 266: 1926-1933.
30 Liu Y, Cao DJ, Sainz IM. et al. The inhibitory effect of HKa in endothelial cell tube formation is mediated by disrupting the uPA-uPAR complex and inhibiting its signaling and internalization. Am J Physiol Cell Physiol 2008; 295: C257-267.
31 Schmaier AH, McCrae KR. The plasma kallikrein-kinin system: its evolution from contact activation. J Thromb Haemost 2007; 5: 2323-2329.
32 Fernando AN, Fernando LP, Fukuda Y. et al. Assembly, activation, and signaling by kinin-forming proteins on human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 2005; 289: H251-257.
33 Herwald H, Hasan AA, Godovac-Zimmermann J. et al. Identification of an endothelial cell binding site on kininogen domain D3. J Biol Chem 1995; 270: 14634-14642.
34 Hasan AA, Cines DB, Herwald H. et al. Mapping the cell binding site on high molecular weight kininogen domain 5. J Biol Chem 1995; 270: 19256-19261.
35 Zini JM, Schmaier AH, Cines DB. Bradykinin regulates the expression of kininogen binding sites on endothelial cells. Blood 1993; 81: 2936-2946.
36 Shariat-Madar Z, Mahdi F, Schmaier AH. Mapping binding domains of kininogens on endothelial cell cytokeratin 1. J Biol Chem 1999; 274: 7137-7145.
37 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 USA 2002; 99: 12224-12229.
38 Herwald H, Renne T, Meijers JC. et al. Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4. J Biol Chem 1996; 271: 13061-13067.
39 Hasan AA, Cines DB, Zhang J. et al. The carboxyl terminus of bradykinin and amino terminus of the light chain of kininogens comprise an endothelial cell binding domain. J Biol Chem 1994; 269: 31822-31830.
40 Dedio J, Muller-Esterl W. Kininogen binding protein p33/gC1qR is localized in the vesicular fraction of endothelial cells. FEBS Lett 1996; 399: 255-258.
41 Dedio J, Jahnen-Dechent W, Bachmann M. et al. The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein. J Immunol 1998; 160: 3534-3542.
42 Jo M, Thomas KS, O’Donnell DM. et al. Epidermal growth factor receptor-dependent and -independent cell-signaling pathways originating from the urokinase receptor. J Biol Chem 2003; 278: 1642-1646.
43 LaRusch GA, Mahdi F, Shariat-Madar Z. et al. Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis. Blood 2010; 115: 5111-5120.
44 Liu Y, Pixley R, Fusaro M. et al. Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway. Oncogene 2009; 28: 2756-2765.
45 Nakazawa YJK, Kaplan AP. Inhibition of contact activation by a kininogen peptide (HK20) derived from domain 5. In: Kinin. 2002. Charleston, South Carolina, USA.: International Immunopharmacology; 2002. pp. 1875-1885.