Abstract

The long term goal of these studies is to understand the structure and function of the von Willebrand receptor GP Ib at a molecular level. This receptor consists of 4 subunits, GP Ib alpha, GP Ib beta, GP IX, and GP V. Shear forces affect the interaction between GP Ib and von Willebrand factor and the first specific aim is to determine whether shear affects GP Ib, von Willebrand factor, or both. Experiments in this specific aim will also characterize the binding domains involved in the shear-induced binding of soluble and immobilized von Willebrand factor to GP Ib. The GP Ib-von Willebrand factor interaction leads to intracellular changes and the second specific aim is to determine how the intracellular domains of the GP Ib complex participate in this transmembrane signaling. The role of GP Ib beta phosphorylation, protein 14-3-3, and actin-binding protein in this signaling will be assessed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039947-12
Application #
6030579
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1988-04-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Yagi, M; Roth, G J (2006) Megakaryocyte polyploidization is associated with decreased expression of polo-like kinase (PLK). J Thromb Haemost 4:2028-34
Bastian, L S; Kwiatkowski, B A; Breininger, J et al. (1999) Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets transcription factor Fli-1. Blood 93:2637-44
Yagi, M; Ritchie, K A; Sitnicka, E et al. (1999) Sustained ex vivo expansion of hematopoietic stem cells mediated by thrombopoietin. Proc Natl Acad Sci U S A 96:8126-31
Yagi, M; Zieger, B; Roth, G J et al. (1998) Structure and expression of the human septin gene HCDCREL-1. Gene 212:229-36
Calverley, D C; Kavanagh, T J; Roth, G J (1998) Human signaling protein 14-3-3zeta interacts with platelet glycoprotein Ib subunits Ibalpha and Ibbeta. Blood 91:1295-303
Li, C; Pasquale, D N; Roth, G J (1996) Bernard-Soulier syndrome with severe bleeding: absent platelet glycoprotein Ib alpha due to a homozygous one-base deletion. Thromb Haemost 76:670-4
Bastian, L S; Yagi, M; Chan, C et al. (1996) Analysis of the megakaryocyte glycoprotein IX promoter identifies positive and negative regulatory domains and functional GATA and Ets sites. J Biol Chem 271:18554-60
Roth, G J (1996) Molecular defects in the Bernard-Soulier syndrome: assessment of receptor genes, transcripts and proteins. C R Acad Sci III 319:819-26
Roth, G J; Yagi, M; Bastian, L S (1996) The platelet glycoprotein Ib-V-IX system: regulation of gene expression. Stem Cells 14 Suppl 1:188-93
Yagi, M; Edelhoff, S; Disteche, C M et al. (1995) Human platelet glycoproteins V and IX: mapping of two leucine-rich glycoprotein genes to chromosome 3 and analysis of structures. Biochemistry 34:16132-7

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