Abstract

The four specific aims are to [1] elucidate the cellular biology of Ts1 and LRP by identifying structural domains of Ts1 that define LRP recognition, [2] define the structural determinants of Ts1 which allow RAP to regulate by LRP, [3] elucidate the mechanisms by which RAP regulates activity of LRP within the cell, and [4] define routes of intercellular trafficking of both LRP and RAP. These studies will have broad implications for understanding the normal and pathophysiological alterations which occur in developing vasculature.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL052040-07
Application #
6183446
Study Section
Pathology A Study Section (PTHA)
Project Start
1997-04-15
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2002-03-31
Support Year
7
Fiscal Year
2000
Total Cost
$283,869
Indirect Cost

  Institution

Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Narita, M; Rudolph, A E; Miletich, J P et al. (1998) The low-density lipoprotein receptor-related protein (LRP) mediates clearance of coagulation factor Xa in vivo. Blood 91:555-60
Warshawsky, I; Herz, J; Broze Jr, G J et al. (1996) The low density lipoprotein receptor-related protein can function independently from heparan sulfate proteoglycans in tissue factor pathway inhibitor endocytosis. J Biol Chem 271:25873-9
Warshawsky, I; Schwartz, A L (1996) The 39-kDa protein regulates LRP activity in cultured endothelial and smooth muscle cells. Eur J Cell Biol 69:156-65
Warshawsky, I; Bu, G; Mast, A et al. (1995) The carboxy terminus of tissue factor pathway inhibitor is required for interacting with hepatoma cells in vitro and in vivo. J Clin Invest 95:1773-81
Narita, M; Bu, G; Olins, G M et al. (1995) Two receptor systems are involved in the plasma clearance of tissue factor pathway inhibitor in vivo. J Biol Chem 270:24800-4
Bu, G; Geuze, H J; Strous, G J et al. (1995) 39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein. EMBO J 14:2269-80
Nielsen, M S; Nykjaer, A; Warshawsky, I et al. (1995) Analysis of ligand binding to the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that lipoprotein lipase and the carboxyl-terminal domain of the receptor-associated protein bind to the same site. J Biol Chem 270:23713-9
Warshawsky, I; Bu, G; Schwartz, A L (1995) Sites within the 39-kDa protein important for regulating ligand binding to the low-density lipoprotein receptor-related protein. Biochemistry 34:3404-15
Narita, M; Bu, G; Herz, J et al. (1995) Two receptor systems are involved in the plasma clearance of tissue-type plasminogen activator (t-PA) in vivo. J Clin Invest 96:1164-8
Bu, G; Maksymovitch, E A; Nerbonne, J M et al. (1994) Expression and function of the low density lipoprotein receptor-related protein (LRP) in mammalian central neurons. J Biol Chem 269:18521-8

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