Cloning of Porcine Platelet Glycoprotein Ibα and Comparison with the Human Homolog

摘要

GlycoproteinIb#8211;IX#8211;V(GPIb#8211;IX#8211;V)isaplateletadhesionreceptorcomplexthatinitiatesplateletaggregation.GlycoproteinIb#945;(GPIb#945;)isthecentralcomponentoftheGPIb#8211;IX#8211;Vcomplex,anchoringthecomplextothecytoskeletonandharboringthebindingsiteforvonWillebrandfactor(vWF).Previousstudiessuggestthatthecoagulationfunctioninpigsdiffersfromthatinhumans,especiallywithrespecttotheinteractionbetweenvWFandplatelets.However,wehavelittleknowledgeaboutthefunctionofporcineplatelets,whichisimportantwithregardtostudiesofcardiovasculardisease,clotting,andsurgerythatusepigsasanimalmodels.Toextendthisinformation,weclonedandanalyzedtheporcineGPIb#945;sequence.PorcineGPIb#945;contains1891nucleotidesandincludesanopenreadingframethatencodes627aminoacids.Thenucleotidesequenceshowed67%identitywithhumanGPIb#945;,whereasthededucedaminoacidsequenceswere59%identical.ThevWFbindingdomainsharesthehighestidentityamongdifferentspecies,whereasthePESTdomainshowsvariations.Evaluationofplateletfunctionbyusingristocetin-inducedplateletaggregationrevealedremarkablylowerlevelsofaggregationinporcinethanhumanplatelets.Accordingtothesequenceanalysisandplateletaggregationtests,weproposethatthefunctionofGPIb#945;,especiallyregardingtheristocetin#8211;vWF#8211;GPIb#945;interaction,differsbetweenpigsandhumans.ThischaracterizationofporcineGPIb#945;willenhanceourknowledgeoftheporcinecoagulationsystem.