|
|
Blood, 15 October 2003, Vol. 102, No. 8, pp. 2811-2818.
Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-01-0231.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
GPVI levels in platelets: relationship to platelet function at high shear
Denise Best,
Yotis A. Senis,
Gavin E. Jarvis,
Helen J. Eagleton,
David J. Roberts,
Takashi Saito,
Stephanie M. Jung,
Masaaki Moroi,
Paul Harrison,
Fiona R. Green, and
Steve P. Watson
From the Department of Pharmacology, Oxford University, Oxford, United Kingdom; the Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom; the Department of Haematology, The John Radcliffe Hospital, Oxford; United Kingdom; the National Blood Service Oxford-Centre, John Radcliffe Hospital, Headington Oxford, United Kingdom; the Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba, Japan; the Laboratory of Cell Signalling, Riken Center for Allergy and Immunology, Yokohama, Japan; the Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume, Japan; Oxford Haemophilia Centre, The Churchill Hospital, Oxford; and the Department of Cardiovascular Medicine, Wellcome Trust Center for Human Genetics, Oxford, United Kingdom.
We have investigated the density of the collagen receptors glycoprotein VI (GPVI) and  2 1 on human platelets and their relationship to polymorphisms within the GPVI gene. GPVI levels varied 1.5-fold and showed a weak correlation (r = 0.35) with the levels of 21, which varied 3-fold. GPVI genotype had a significant effect on receptor levels with carriers of the proline 219 allele (approximately 22% of the population) having 10% lower GPVI levels than the more common serine homozygotes. GPVI and 21 levels were found to be significantly decreased on platelets from patients with myeloproliferative disorders (MPDs). In both the MPD and the control group, GPVI levels were found not to affect platelet function under high shear in whole blood. Similarly murine platelets that express up to 5-fold lower levels of GPVI showed no significant difference than controls in thrombus formation on a high-density collagen-coated surface. However platelets lacking the GPVI/Fc receptor  -chain (FcR -chain) complex or a functional FcR -chain (immunoreceptor tyrosine-based activation motif [ITAM] point mutant) exhibited severely abrogated thrombus formation at 800 s–1 and 1500 s–1. These results demonstrate that GPVI levels are tightly controlled and play a critical role in thrombus formation on collagen; nevertheless, a range of receptor densities can support platelet function under high shear.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Trifiro, S. A. Williams, Y. Cheli, K. Furihata, F. M. Pulcinelli, D. J. Nugent, and T. J. Kunicki
The low-frequency isoform of platelet glycoprotein VIb attenuates ligand-mediated signal transduction but not receptor expression or ligand binding
Blood,
August 27, 2009;
114(9):
1893 - 1899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. A. Senis, M. G. Tomlinson, S. Ellison, A. Mazharian, J. Lim, Y. Zhao, K. N. Kornerup, J. M. Auger, S. G. Thomas, T. Dhanjal, et al.
The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis
Blood,
May 14, 2009;
113(20):
4942 - 4954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Auger and S. P. Watson
Dynamic Tyrosine Kinase-Regulated Signaling and Actin Polymerisation Mediate Aggregate Stability Under Shear
Arterioscler Thromb Vasc Biol,
August 1, 2008;
28(8):
1499 - 1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Rabie, D. Varga-Szabo, M. Bender, R. Pozgaj, F. Lanza, T. Saito, S. P. Watson, and B. Nieswandt
Diverging signaling events control the pathway of GPVI down-regulation in vivo
Blood,
July 15, 2007;
110(2):
529 - 535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Andrews, D. Karunakaran, E. E. Gardiner, and M. C. Berndt
Platelet Receptor Proteolysis: A Mechanism for Downregulating Platelet Reactivity
Arterioscler Thromb Vasc Biol,
July 1, 2007;
27(7):
1511 - 1520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. A. Senis, M. G. Tomlinson, A. Garcia, S. Dumon, V. L. Heath, J. Herbert, S. P. Cobbold, J. C. Spalton, S. Ayman, R. Antrobus, et al.
A Comprehensive Proteomics and Genomics Analysis Reveals Novel Transmembrane Proteins in Human Platelets and Mouse Megakaryocytes Including G6b-B, a Novel Immunoreceptor Tyrosine-based Inhibitory Motif Protein
Mol. Cell. Proteomics,
March 1, 2007;
6(3):
548 - 564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. F. Bray, T. D. Howard, E. Vittinghoff, D. C. Sane, and D. M. Herrington
Effect of genetic variations in platelet glycoproteins Ib{alpha} and VI on the risk for coronary heart disease events in postmenopausal women taking hormone therapy
Blood,
March 1, 2007;
109(5):
1862 - 1869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. F. Samaha and M. L. Kahn
Novel Platelet and Vascular Roles for Immunoreceptor Signaling
Arterioscler Thromb Vasc Biol,
December 1, 2006;
26(12):
2588 - 2593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. J. T. McCarty, M. K. Larson, J. M. Auger, N. Kalia, B. T. Atkinson, A. C. Pearce, S. Ruf, R. B. Henderson, V. L. J. Tybulewicz, L. M. Machesky, et al.
Rac1 Is Essential for Platelet Lamellipodia Formation and Aggregate Stability under Flow
J. Biol. Chem.,
November 25, 2005;
280(47):
39474 - 39484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Kunicki, Y. Cheli, M. Moroi, and K. Furihata
The influence of N-linked glycosylation on the function of platelet glycoprotein VI
Blood,
October 15, 2005;
106(8):
2744 - 2749.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Sarratt, H. Chen, M. M. Zutter, S. A. Santoro, D. A. Hammer, and M. L. Kahn
GPVI and {alpha}2{beta}1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow
Blood,
August 15, 2005;
106(4):
1268 - 1277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Hughan, Y. Senis, D. Best, A. Thomas, J. Frampton, P. Vyas, and S. P. Watson
Selective impairment of platelet activation to collagen in the absence of GATA1
Blood,
June 1, 2005;
105(11):
4369 - 4376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Stephens, Y. Yan, M. Jandrot-Perrus, J.-L. Villeval, K. J. Clemetson, and D. R. Phillips
Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen
Blood,
January 1, 2005;
105(1):
186 - 191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Pearce, Y. A. Senis, D. D. Billadeau, M. Turner, S. P. Watson, and E. Vigorito
Vav1 and Vav3 Have Critical but Redundant Roles in Mediating Platelet Activation by Collagen
J. Biol. Chem.,
December 24, 2004;
279(52):
53955 - 53962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lecut, A. Schoolmeester, M. J.E. Kuijpers, J. L.V. Broers, M. A.M.J. van Zandvoort, K. Vanhoorelbeke, H. Deckmyn, M. Jandrot-Perrus, and J. W.M. Heemskerk
Principal Role of Glycoprotein VI in {alpha}2{beta}1 and {alpha}IIb{beta}3 Activation During Collagen-Induced Thrombus Formation
Arterioscler Thromb Vasc Biol,
September 1, 2004;
24(9):
1727 - 1733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Cabeza, Z. Li, C. Schulz, E. Kremmer, S. Massberg, A. Bultmann, and M. Gawaz
Surface Expression of Collagen Receptor Fc Receptor-{gamma}/Glycoprotein VI Is Enhanced on Platelets in Type 2 Diabetes and Mediates Release of CD40 Ligand and Activation of Endothelial Cells
Diabetes,
August 1, 2004;
53(8):
2117 - 2121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. E. Kuijpers, V. Schulte, C. Oury, T. Lindhout, J. Broers, M. F. Hoylaerts, B. Nieswandt, and J. W. M. Heemskerk
Facilitating roles of murine platelet glycoprotein Ib and {alpha}IIb{beta}3 in phosphatidylserine exposure during vWF-collagen-induced thrombus formation
J. Physiol.,
July 15, 2004;
558(2):
403 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Marshall, Y. A. Senis, J. M. Auger, R. Feil, F. Hofmann, G. Salmon, J. T. Peterson, F. Burslem, and S. P. Watson
GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase
Blood,
April 1, 2004;
103(7):
2601 - 2609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
