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Título: | Role of the α-subunit 326GRV sequence in the surface expression of fibrinogen and vitronectin receptors |
Autor: | Ferrer, Milagros CSIC; Sánchez Ayuso, Matilde CSIC ORCID ; Butta, Nora CSIC ORCID; Parrilla, Roberto L.; González-Manchón, Consuelo CSIC ORCID | Palabras clave: | GPIIb GPIIb-IIIa Integrins Mutagenesis |
Fecha de publicación: | 1-nov-1998 | Editor: | American Physiological Society | Citación: | American Journal of Physiology - Cell Physiology 275(5): C1239-C1246 (1998) | Resumen: | The platelet GPIIb-GPIIIa heterodimer (integrin α(IIb)β3) binds fibrinogen with high affinity in response to activation by agonists, leading to platelet aggregation and formation of a hemostatic plug. The 326GRV motif in GPIIb is highly conserved in the α-subunit of other integrins, suggesting that it might play an important functional role. Moreover, Arg327→His substitution in GPIIb has been associated with defective platelet surface expression of GPIIb-IIIa and thrombasthenic phenotype. This work aimed at elucidating whether the absence of Arg327 or its substitution by His was responsible for the impaired surface expression of GPIIb-IIIa complexes. Transfection of cDNA encoding [Ala327]GPIIb, [Gln327]GPIIb, or [Phe327]GPIIb into Chinese hamster ovary cells inherently expressing GPIIIa permitted surface exposure of GPIIb-IIIa complexes, whereas [Glu327]GPIIb did not. These observations indicate that it is not the loss of [Arg327]GPIIb but the presence of His327 or a negatively charged residue like Glu at position 327 of GPIIb that prevents the surface exposure of GPIIb-IIIa heterodimers. In contrast, changing Gln344, the homologue to Arg327 in the α-subunit of the vitronectin receptor, to His did not prevent the surface expression of α(v)-GPIIIa complexes. Thus the conformational constraint imposed by His327 seems to be rather specific for the heterodimerization and/or processing of GPIIb- IIIa complexes. | Versión del editor: | https://doi.org/10.1152/ajpcell.1998.275.5.C1239 | URI: | http://hdl.handle.net/10261/226375 | DOI: | 10.1152/ajpcell.1998.275.5.C1239 | Identificadores: | doi: 10.1152/ajpcell.1998.275.5.C1239 issn: 0363-6143 |
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