Abstract

The proposal addresses the problem of how platelet surface glycoprotein Ib-IX (the receptor for von Willebrand factor) signals to activate the platelet following GPIb-vWf interaction. Progress has been made recently by the PI in identifying and characterizing a protein (29kDa) that is associated with GPIb-IX. The protein has been identified as P29, a modifier of protein kinase C, also termed a x-form of 14-3-3 which has phospholipase A2 activity. The proposal sets out to characterize the interaction between 14-3-3 and GP Ib-IX and to characterize the functions of 14-3-3. Specifically, four aims are proposed: first, further characterize the interaction between GPIb-IX and 14-3-3, second, examine the functions of P29 and how it is modulated by ligand binding to GPIIb-IX, third, characterize and express the phosholipase activity of P29, fourth, characterize the structural basis of the interaction between GPIb-IX and P29.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL052547-05
Application #
2702252
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1995-05-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Pharmacology
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Bodnar, Richard J; Yates, Cecelia C; Rodgers, Margaret E et al. (2009) IP-10 induces dissociation of newly formed blood vessels. J Cell Sci 122:2064-77
Li, Z; Xi, X; Du, X (2001) A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin alpha IIbbeta3. J Biol Chem 276:42226-32
Englund, G D; Bodnar, R J; Li, Z et al. (2001) Regulation of von Willebrand factor binding to the platelet glycoprotein Ib-IX by a membrane skeleton-dependent inside-out signal. J Biol Chem 276:16952-9
Pfaff, M; Du, X; Ginsberg, M H (1999) Calpain cleavage of integrin beta cytoplasmic domains. FEBS Lett 460:17-22
Bodnar, R J; Gu, M; Li, Z et al. (1999) The cytoplasmic domain of the platelet glycoprotein Ibalpha is phosphorylated at serine 609. J Biol Chem 274:33474-9
Gu, M; Xi, X; Englund, G D et al. (1999) Analysis of the roles of 14-3-3 in the platelet glycoprotein Ib-IX-mediated activation of integrin alpha(IIb)beta(3) using a reconstituted mammalian cell expression model. J Cell Biol 147:1085-96
Gu, M; Du, X (1998) A novel ligand-binding site in the zeta-form 14-3-3 protein recognizing the platelet glycoprotein Ibalpha and distinct from the c-Raf-binding site. J Biol Chem 273:33465-71
Meredith Jr, J; Mu, Z; Saido, T et al. (1998) Cleavage of the cytoplasmic domain of the integrin beta3 subunit during endothelial cell apoptosis. J Biol Chem 273:19525-31
Du, X; Fox, J E; Pei, S (1996) Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha. J Biol Chem 271:7362-7
Du, X; Saido, T C; Tsubuki, S et al. (1995) Calpain cleavage of the cytoplasmic domain of the integrin beta 3 subunit. J Biol Chem 270:26146-51

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