Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib

SummaryThe main question concerning the mechanism of α-thrombin binding to platelet membrane glycoprotein (GP)Ib is whether it involves both thrombin exosite I and exosite II. The solution of two independent crystal structures suggests alternative explanations that may actually reflect different modes of binding with distinct pathophysiological significance. With respect to function, it is still unclear whether thrombin binding to GPIb promotes procoagulant and prothrombotic pathways of re-sponse to vascular injury or limits such responses by sequestering, at least temporarily, the active enzyme. We review here published information on these topics and touch upon ongoing studies aimed at finding definitive answers to outstanding questions relevant for a better understanding of thrombosis and haemostasis.

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Residual amounts of glycoprotein Ib concomitant with near-absence of glycoprotein IX in platelets of Bernard-Soulier patients

Blood ◽

10.1182/blood.v72.3.1086.bloodjournal7231086 ◽

1988 ◽

Vol 72 (3) ◽

pp. 1086-1088 ◽

Cited By ~ 18

Author(s):

J Drouin ◽

JL McGregor ◽

S Parmentier ◽

CA Izaguirre ◽

KJ Clemetson

Keyword(s):

Normal Level ◽

Polyclonal Antibodies ◽

Band Pattern ◽

Platelet Membrane ◽

Membrane Glycoprotein ◽

Glycoprotein Ib ◽

Gene Deletions ◽

Immunoblot Assay ◽

Platelet Membrane Glycoprotein ◽

Bernard Soulier Syndrome

A study of the Bernard-Soulier syndrome in two unrelated families using different polyclonal antibodies in a sensitive immunoblot assay showed residual amounts of platelet membrane glycoprotein (GP) lb in the eight homozygotes, as well as the near-absence of GPlb beta and GPIX. The eight heterozygotes studied showed a double band pattern for GPlb and about half the normal level of GPlb beta and GPIX. Therefore, we conclude that the Bernard-Soulier syndrome is heterogeneous and is probably not due to gene deletions.

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Binding of Heparin to Platelet Membrane Glycoprotein Ib: Functional Effects

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614465 ◽

1999 ◽

Vol 81 (02) ◽

pp. 316-317 ◽

Cited By ~ 5

Author(s):

K. J. Clemetson ◽

M.-C. Guillin ◽

M.-C. Bouton ◽

M. Jandrot-Perrus

Keyword(s):

Platelet Membrane ◽

Membrane Glycoprotein ◽

Glycoprotein Ib ◽

Platelet Membrane Glycoprotein

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Polymorphisms of Platelet Membrane Glycoprotein Ib Associated With Arterial Thrombotic Disease

Blood ◽

10.1182/blood.v92.8.2771 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2771-2776 ◽

Cited By ~ 115

Author(s):

Rocio Gonzalez-Conejero ◽

Maria L. Lozano ◽

Jose Rivera ◽

Javier Corral ◽

Juan A. Iniesta ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Venous Thrombosis ◽

Platelet Membrane ◽

Membrane Glycoprotein ◽

Glycoprotein Ib ◽

Initial Development ◽

Thrombotic Disease ◽

Platelet Membrane Glycoprotein ◽

Increased Risk

Abstract Platelet membrane glycoprotein Ib (GPIb) is a major receptor for von Willebrand factor and thrombin, which plays a key role in the initial development of thrombi. Two polymorphisms (HPA-2 and VNTR) that affect phenotype have been described in GPIb. The relevance of these polymorphisms to thrombotic disease was investigated by genotypic identification in three case-control studies: 104 case patients with acute cerebrovascular disease (CVD), 101 case patients with acute coronary heart disease (CHD), 95 patients with deep venous thrombosis (DVT), and one control age-, sex-, and race-matched for each case patient. Results show that the C/B genotype of the VNTR and the HPA-2b polymorphisms of GPIb are strongly associated with increased risk of coronary heart disease and cerebral vascular disease but not with deep vein thrombosis. These two polymorphisms of GPIb may represent newly identified risk factors for arterial thrombotic disease, but not for venous thrombosis. © 1998 by The American Society of Hematology.

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