scholarly journals Novel heterozygous missense mutation in the platelet glycoprotein Ib? gene associated with isolated giant platelet disorder

2001 ◽  
Vol 68 (4) ◽  
pp. 249-255 ◽  
Author(s):  
Shinji Kunishima ◽  
Tomoki Naoe ◽  
Tadashi Kamiya ◽  
Hidehiko Saito
Keyword(s):  
Missense Mutation ◽  
Platelet Glycoprotein ◽  
Glycoprotein Ib ◽  
Heterozygous Missense Mutation ◽  
Giant Platelet ◽  
Platelet Disorder

A Missense Mutation (Tyr88 to Cys) in the Platelet Membrane Glycoprotein Ibβ Gene Affects GPIb/IX Complex Expression

2001 ◽  
Vol 86 (11) ◽  
pp. 1249-1256 ◽  
Author(s):  
Yumi Kurokawa ◽  
Takehiko Kamijo ◽  
Shinji Kunishima ◽  
Dermot Kenny ◽  
Kiyoshi Kitano ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Platelet Glycoprotein ◽  
Homozygous Mutation ◽  
Sequencing Analysis ◽  
Giant Platelets ◽  
Giant Platelet ◽  
Negative Effect ◽  
Dna Sequencing Analysis

SummaryThis study examined the molecular basis of a missense mutation of the platelet glycoprotein (GP) Ibβ gene in two families. In the propositus with a novel form of Bernard-Soulier syndrome (BSS) from Family I, only GPIbα was detectable in reduced amounts on platelet surfaces by flow cytometry. There were no GPIX or GPIbβ found by immunoblotting. DNA sequencing analysis showed a homozygous mutation in the GPIbβ gene which changed Tyr (TAC) to Cys (TGC) at residue 88. Her parents were heterozygous for Tyr88Cys in the GPIbβ gene. In transient transfection studies on 293T cells, both Tyr88Cys and Tyr88Ala mutations suppressed the expression of GPIb/IX complexes. In addition, Tyr88Cys GPIbβ mutation was found to exert a dominant negative effect on the GPIb expression.Five individuals from Family II, four of whom reported elsewhere as having giant platelet disorders with normal aggregation (BLOOD, 1997; 89: 2404) and one newly analyzed in this study, were heterozygous for Tyr88Cys in the GPIb gene. Microsatellite analysis of chromosome 22 showed a common haplotype in 8 of the individuals with Tyr88Cys mutations in Families I and II. Tyr88 in the GPIbβ gene plays a significant role in the GPIb/IX expression; the defect causes BSS in a homozygous form and possibly giant platelets in a heterozygous form.

Glycoprotein Ib Can Mediate Endothelial Cell Attachment to a von Willebrand Factor Substratum

1995 ◽  
Vol 73 (02) ◽  
pp. 309-317 ◽  
Author(s):  
Dorothy A Beacham ◽  
Miguel A Cruz ◽  
Robert I Handin
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Attachment ◽  
Umbilical Vein ◽  
Single Amino Acid ◽  
Cell Surface Expression ◽  
Platelet Glycoprotein ◽  
Glycoprotein Ib ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIntroduction of single amino acid substitutions into the C-terminal Arg-Gly-Asp-Ser (RGDS) site of von Willebrand Factor, referred to as RGD mutant vWF, selectively abrogated vWF binding to platelet glycoprotein IIb/IIIa (GpIIb/IIIa, αIIbβ3 and abolished human umbilical vein endothelial cell (HUVEC) spreading, but not attachment, to RGD mutant vWF (Beacham, D. A., Wise, R. J., Turci, S. M. and Handin, R. I. 1992. J. Biol. Chem. 167, 3409-3415). These results suggested that in addition to the vitronectin receptor (VNR, αvβ3), a second endothelial membrane glycoprotein can mediate HUVEC adhesion to vWF. HUVEC attachment to wild-type (WT) and RGD-mutant vWF was reduced by two proteins known to block the vWF-platelet glycoprotein Ib/IX (GpIb/IX) interaction, the monoclonal antibody AS-7 and the recombinant polypeptide, vWF-A1. The addition of cytochalasin B or DNase I to disrupt potential GPIbα-cytoskeletal interactions enhanced the immunoprecipitation of endothelial GPIbα, caused HUVEC to round up, and increased HUVEC adhesion to RGD mutant vWF. These results indicate that while the VNR is the primary adhesion receptor for vWF, endothelial GPIbα can mediate HUVEC attachment to vWF. GpIb-dependent attachment could contribute to HUVEC adhesion under conditions when cell surface expression of the VNR is downregulated, and VNR-dependent adhesion is reduced.

scholarly journals Role for Platelet Glycoprotein Ib-IX and Effects of its Inhibition in Endotoxemia-Induced Thrombosis, Thrombocytopenia, and Mortality

2013 ◽  
Vol 33 (11) ◽  
pp. 2529-2537 ◽  
Author(s):  
Hong Yin ◽  
Aleksandra Stojanovic-Terpo ◽  
Weidong Xu ◽  
Adam Corken ◽  
Alexander Zakharov ◽  
...  
Keyword(s):  
Platelet Glycoprotein ◽  
Glycoprotein Ib
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