Abstract

Protein Z is a vitamin K-dependent plasma protein of previously unknown function. The goals of this proposal are to biochemically characterize: 1) the interaction between protein Z and factor Xa at the surface of phospholipids; 2) the protein mediated enhancement of factor Xa inhibition by tissue factor pathway inhibitor; and 3) the protein Z-dependent inhibition of factor Xa produced by an additional, previously unrecognized plasma protein. In additional studies, the in vivo consequences of protein Z deficiency will be determined in mice. The experiments are designed to provide information, now lacking, concerning the function of protein Z. These results should enhance our understanding of both hemostasis and pathological thromboembolism.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060782-03
Application #
6184652
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1998-09-08
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
3
Fiscal Year
2000
Total Cost
$332,019
Indirect Cost

  Institution

Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110

  Publications

Butschkau, Antje; Nagel, Philipp; Grambow, Eberhard et al. (2013) Contribution of protein Z and protein Z-dependent protease inhibitor in generalized Shwartzman reaction. Crit Care Med 41:e447-56
Girard, T J; Lasky, N M; Tuley, E A et al. (2013) Protein Z, protein Z-dependent protease inhibitor (serpinA10), and the acute-phase response. J Thromb Haemost 11:375-8
Huang, Xin; Yan, Yahui; Tu, Yizheng et al. (2012) Structural basis for catalytic activation of protein Z-dependent protease inhibitor (ZPI) by protein Z. Blood 120:1726-33
Sofi, Francesco; Cesari, Francesca; Abbate, Rosanna et al. (2010) A meta-analysis of potential risks of low levels of protein Z for diseases related to vascular thrombosis. Thromb Haemost 103:749-56
Broze Jr, G J; Tu, Y (2010) Protein Z and protein Z-dependent protease inhibitor and renal tubules. Thromb Haemost 103:473-4
Sofi, F; Cesari, F; Tu, Y et al. (2009) Protein Z-dependent protease inhibitor and protein Z in peripheral arterial disease patients. J Thromb Haemost 7:731-5
Zhang, Jing; Tu, Yizheng; Lu, Lan et al. (2008) Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency. Blood 111:4973-8
Piro, O; Broze Jr, G J (2005) Comparison of cell-surface TFPIalpha and beta. J Thromb Haemost 3:2677-83
Piro, Orlando; Broze Jr, George J (2004) Role for the Kunitz-3 domain of tissue factor pathway inhibitor-alpha in cell surface binding. Circulation 110:3567-72
Zhang, Jing; Piro, Orlando; Lu, Lan et al. (2003) Glycosyl phosphatidylinositol anchorage of tissue factor pathway inhibitor. Circulation 108:623-7

Showing the most recent 10 out of 12 publications