|
|
 Previous Article | Table of Contents | Next Article 
Expression and Functional Characterization of an Abnormal Platelet Membrane Glycoprotein Ib (Met239  Val) Reported in Patients With Platelet-Type von Willebrand Disease
Takanori Moriki,
Mitsuru Murata,
Tetsuya Kitaguchi,
Hironobu Anbo,
Makoto Handa,
Kiyoaki Watanabe,
Hoyu Takahashi, and
Yasuo Ikeda
From the Departments of Internal Medicine, Blood Center, and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan; and the Blood Transfusion Division, Niigata University School of Medicine, Niigata, Japan.
Platelet-type von Willebrand disease (vWD) is a congenital bleeding disorder characterized by heightened ristocetin-induced platelet aggregation caused by abnormally high affinity between the platelet membrane glycoprotein (GP) Ib/IX complex and von Willebrand factor (vWF ). Two distinct point mutations, Gly233 to Val and Met239 to Val, have been reported in GPIb . We have constructed a recombinant GPIb fragment containing the latter mutation, Met239 to Val (M239V) and characterized the mutant molecule using two methods, ie, interaction between soluble vWF and immobilized M239V and inhibition of platelet aggregation by purified soluble M239V. Spontaneous binding (ie, binding without any inducers) was observed between 125I-vWF and immobilized M239V but not between 125I-vWF and immobilized wild-type (WT) GPIb. The addition of low concentrations of ristocetin (0.2 mg/mL) induced specific 125I-vWF binding to immobilized M239V, but not to WT GPIb. At high concentrations of ristocetin (1.2 mg/mL), both WT GPIb and M239V specifically bound to 125I-vWF. Thus, M239V reproduced the unique functional abnormality of the GPIb/IX complex in platelet-type vWD. Moreover, the purified soluble M239V inhibited platelet aggregation induced by low concentration of ristocetin (0.3 mg/mL) in platelet-rich plasma from a patient having Met239 to Val mutation, whereas purified WT did not. These results provide direct evidences that the reported point mutation is the responsible molecular basis of this disorder.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 698-705
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Lou and C. Zhu
Flow induces loop-to-{beta}-hairpin transition on the {beta}-switch of platelet glycoprotein Ib{alpha}
PNAS,
September 16, 2008;
105(37):
13847 - 13852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Suva, E. Hartman, J. D. Dilley, S. Russell, N. S. Akel, R. A. Skinner, W. R. Hogue, U. Budde, K. I. Varughese, T. Kanaji, et al.
Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease
Am. J. Pathol.,
February 1, 2008;
172(2):
430 - 439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Othman, C. Notley, F. L. Lavender, H. White, C. D. Byrne, D. Lillicrap, and D. F. O'Shaughnessy
Identification and functional characterization of a novel 27-bp deletion in the macroglycopeptide-coding region of the GPIBA gene resulting in platelet-type von Willebrand disease
Blood,
June 1, 2005;
105(11):
4330 - 4336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Dumas, R. Kumar, T. McDonagh, F. Sullivan, M. L. Stahl, W. S. Somers, and L. Mosyak
Crystal Structure of the Wild-type von Willebrand Factor A1-Glycoprotein Ib{alpha} Complex Reveals Conformation Differences with a Complex Bearing von Willebrand Disease Mutations
J. Biol. Chem.,
May 28, 2004;
279(22):
23327 - 23334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Tait, S. L. Cranmer, S. P. Jackson, I. W. Dawes, and B. H. Chong
Phenotype changes resulting in high-affinity binding of von Willebrand factor to recombinant glycoprotein Ib-IX: analysis of the platelet-type von Willebrand disease mutations
Blood,
September 15, 2001;
98(6):
1812 - 1818.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Katayama, Y. Ikeda, M. Handa, T. Tamatani, S. Sakamoto, M. Ito, Y. Ishimura, and M. Suematsu
Immunoneutralization of Glycoprotein Ib{alpha} Attenuates Endotoxin-Induced Interactions of Platelets and Leukocytes With Rat Venular Endothelium In Vivo
Circ. Res.,
May 26, 2000;
86(10):
1031 - 1037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-f. Dong, A. J. Schade, G. M. Romo, R. K. Andrews, S. Gao, L. V. McIntire, and J. A. Lopez
Novel Gain-of-function Mutations of Platelet Glycoprotein Ibalpha by Valine Mutagenesis in the Cys209-Cys248 Disulfide Loop. FUNCTIONAL ANALYSIS UNDER STATIC AND DYNAMIC CONDITIONS
J. Biol. Chem.,
September 1, 2000;
275(36):
27663 - 27670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
