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pubmed-article:14675101pubmed:abstractTextThe platelet receptor GPIb/IX/V mediates a crucial role in hemostasis, yet the signaling mechanisms involved are incompletely understood. The complex consists of four polypeptides GPIb alpha, GPIb beta, GPIX and GPV. We identified an amino acid sequence in the cytoplasmic tail of the GPIb beta subunit between residues R151 and A161 that is highly conserved across species and hypothesized that it has functional importance. To target this motif, we synthesized a corresponding cell-permeable palmitylated peptide (Pal-RRLRARARARA) and investigated its effect on platelet function. Pal-RRLRARARARA completely inhibited low dose thrombin- and ristocetin-induced aggregation in washed platelets but only partially inhibited collagen- and U46619-induced aggregation. Thromboxane production in platelets stimulated with thrombin was significantly reduced by Pal-RRLRARARARA compared with collagen. Activation of the integrin alpha IIb beta 3 in response to thrombin was significantly reduced when platelets were preincubated with Pal-RRLRARARARA. The adhesion of washed platelets to von Willebrand factor (VWF) under static conditions was significantly reduced by Pal-RRLRARARARA. Under conditions of high shear, the velocity of platelets rolling on VWF was significantly increased when platelets are preincubated with Pal-RRLRARARARA. This study defines a novel function for the RRLRARARARA motif of GPIb beta in platelet activation.lld:pubmed
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pubmed-article:14675101pubmed:authorpubmed-author:MartinKKlld:pubmed
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pubmed-article:14675101pubmed:pagination2643-52lld:pubmed
pubmed-article:14675101pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:14675101pubmed:articleTitleA palmitylated peptide derived from the glycoprotein Ib beta cytoplasmic tail inhibits platelet activation.lld:pubmed
pubmed-article:14675101pubmed:affiliationDepartment of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.lld:pubmed
pubmed-article:14675101pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:14675101pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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