Kamata et al. reported that clustering of disulphide bonds in EGF domains is very important for the regulation of ?IIb?3 integrin function . They found that disruption of a single disulphide bond inside the EGF domains was adequate to activate ?IIb?three completely. These results indicate that intact disulphide bonds inside the EGF domains are significant for the preservation the ?IIb?three resting state. Recently, MorCohen et al. demonstrated that disruption on the Cys567Cys581 disulphide bond within the 4th EGFlike domain sustained the inactive state of ?IIb?three integrin, even just after exposure to ?IIb?three activating antibodies, indicating that this disulphide bond is significant for integrin activation . We speculate that the Lys580Asn mutation responsible for the formation of Seca epitopes impairs the adjacent Cys567Cys581 and/or Cys583Cys560 disulphide bonds, altering the activation capability of ?IIb?three integrin; a phenomenon, which we observed with our transfected cells expressing the ?3 Asn580 isoform.
The role of one particular polymorphism get more information residing on ?three, Leu33Pro , has been studied intensively as genetic risk issue for arterial thrombosis inside the last decade. Contradictory outcomes have been observed . Vijayan et al. showed that CHO and human kidney embryonal 293 cells overexpressing the HPA1b bound significantly even more in comparison to HPA1a transfected cells . In our study, on the other hand, no difference within the adhesion capacity onto fibrinogen was observed among HPA1a and HPA1b transfected cells, while each cells had comparable ?IIb?three surface expression . Current information indicated that glutathione could regulate ?IIb?3mediated cell adhesion beneath flow situations ; enhanced adhesion of HPA1b transfected cells was only observed inside the absence of reduced and oxidised glutathione .
This observation indicates that not only the HPA1b phenotype, but additionally the redox state of platelet ?IIb?3 may possibly play a function in the regulation of this critical platelet fibrinogen receptor . The direct impact of the Leu33Pro dimorphismus around the behaviour from the Trihydroxyethylrutin integrin disulphide bonds, even so, is at the moment not identified. Point mutations and deletions responsible for the formation of HPAs on ?3 subunit were discovered in unique domains with the molecule; HPA1 within the PSIdomain; HPA4, ?16, ?17, ? 19 and Mat in the ?Adomain; HPA7, ?10 and Hit in the hybrid domain, and HPA8, ?11, ? 14 and ?2 within the ?tail domain . A few functional research have been performed for many of those HPAs, but none of those mutations appears to alter ?IIb?3 function.
In this study, we identified a polymorphism, Lys480Asn, located around the fourth EGF4 domain of ?three, which can be responsible for the formation of a new rare platelet alloantigen Seca, and which impacts ?IIb?3 function.