Abstract

For Project 2, flow cytometry will be used to determine whether platelet FXI is expressed normally in patients with type II FXI deficiency, and whether platelet FXI can substitute for plasma FXI in platelet activation. Flow cytometry will also be used to verify recombinant co-expression of GPIbalpha, GPIbbeta, GPIX and platelet FXI on the surface of CHO and L-cells. For Project 3, flow cytometry will be used to study the expression of GPIIB-IIIA in platelets, in response to several G-protein coupled receptors (ADP, PAF, thrombin, U46619) and cell permeable activations (A23187 and PKC activators). For Project 4, flow cytometry will be used to estimate fibrinogen activation by platelet agonists in normal platelets, platelets from patients with bleeding disorders, and A5 cells under various conditions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL064943-03
Application #
6587890
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
$209,267
Indirect Cost

  Institution

Name
Temple University
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122

  Publications

Hung, Su H; Liu, Andy H; Pixley, Robin A et al. (2008) A new nonhydrolyzable reactive cGMP analogue, (Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate, which targets the cGMP binding site of human platelet PDE3A. Bioorg Chem 36:141-7
Murugappa, Swaminathan; Kunapuli, Satya P (2006) The role of ADP receptors in platelet function. Front Biosci 11:1977-86
Hung, Su-Hwi; Zhang, Wei; Pixley, Robin A et al. (2006) New insights from the structure-function analysis of the catalytic region of human platelet phosphodiesterase 3A: a role for the unique 44-amino acid insert. J Biol Chem 281:29236-44
Yang, Xia; Walsh, Peter N (2005) An ordered sequential mechanism for Factor IX and Factor IXa binding to platelet receptors in the assembly of the Factor X-activating complex. Biochem J 390:157-67
Sinha, Dipali; Marcinkiewicz, Mariola; Lear, James D et al. (2005) Factor XIa dimer in the activation of factor IX. Biochemistry 44:10416-22
Dangelmaier, Carol A; Quinter, Patricia G; Jin, Jianguo et al. (2005) Rapid ubiquitination of Syk following GPVI activation in platelets. Blood 105:3918-24
Dorsam, Robert T; Kim, Soochong; Murugappan, Swaminathan et al. (2005) Differential requirements for calcium and Src family kinases in platelet GPIIb/IIIa activation and thromboxane generation downstream of different G-protein pathways. Blood 105:2749-56
Quinton, T M; Kim, S; Jin, J et al. (2005) Lipid rafts are required in Galpha(i) signaling downstream of the P2Y12 receptor during ADP-mediated platelet activation. J Thromb Haemost 3:1036-41
Wakabayashi, Hironao; Su, Ya-Chi; Ahmad, Syed S et al. (2005) A Glu113Ala mutation within a factor VIII Ca2+-binding site enhances cofactor interactions in factor Xase. Biochemistry 44:10298-304
Ahmad, Syed S; Walsh, Peter N (2005) Role of the C2 domain of factor VIIIa in the assembly of factor-X activating complex on the platelet membrane. Biochemistry 44:13858-65

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