A mutant (Arg(327)->His) GPIIb associated to thrombasthenia exerts a dominant negative effect in stably transfected CHO cells

作者：Ferrer M; FernandezPinel M; GonzalezManchon C; Gonzalez J; Ayuso MS; Parrilla R

来源：Thrombosis and Haemostasis, 1996, 76(3): 292-301.

This work reports the structural and functional characterization of the platelet glycoprotein complex GPIIb-IIIa (integrin alpha(IIb)beta(3)) in a patient of type II Glanzmann thrombasthenia, bearing a homozygous G-->A base transition at position 1074 of GPIIb that results in an Ar-327-->His substitution.
CHO cells stably transfected with cDNA encoding His(327)GPIIb showed a drastic reduction in the surface expression of alpha(IIb)beta(3) complex relative to control cells transfected with wild type GPIIb. Immunoprecipitation analysis demonstrated that GPIIb synthesis, heterodimerization, and short term maturation were not impeded, suggesting that conformational changes dependent on Ag-327 of GPIIb may play an essential role in either the rare of maturation and/or transport of heterodimers to the cell surface.
Cotransfection of CHO cells with equimolar amounts of cDNAs encoding wild type and mutant His(327)-GPIIb led to a marked reduction in the surface expression of alpha(IIB)beta(3). This novel observation of a dominant-negative effect of the mutant His(327)alpha(IIb), subunit provides a molecular basis for the reduced platelet alpha(IIb)beta(3) content observed in the heterozygous offspring.

• 出版日期1996-9