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- W2148822857 abstract "Glycoprotein (GP) Ib/V/IX complex–dependent platelet adhesion to von Willebrand factor (VWF) is supported by the 45-kd N-terminal extracellular domain of the GPIbα subunit. Recent results with an adhesion blocking antibody (RAM.1) against GPIbβ, which is disulfide linked to GPIbα, have suggested a novel function of this subunit in regulating VWF-mediated platelet adhesion, possibly involving its intracellular face. A putative cooperation between the GPIbα and GPIbβ cytoplasmic domains was investigated by measuring the adhesion under flow to immobilized VWF of K562 and Chinese hamster ovary (CHO) cells transfected with GPIb/(V)/IX containing mutations in this region. Adhesion of cells carrying a glycine substitution of the GPIbβ Ser166 phosphorylation site was 50% lower than normal and became insensitive to inhibition by RAM.1. In contrast, forskolin or PGE1 treatment increased both the phosphorylation of GPIbβ and adhesion of control cells, both effects being reversed by RAM.1, but had no influence on cells expressing the Ser166Gly mutation. A role of the GPIbα intracellular domain was also apparent as the VWF-dependent adhesion of cells containing deletions of the entire (Δ518-610) or portions (Δ535-568, Δ569-610) of the GPIbα cytoplasmic tail was insensitive to RAM.1 inhibition. Cells carrying progressive 11 amino acid deletions spanning the GPIbα 535-590 region were equally unresponsive to RAM.1, with the exception of those containing GPIbα Δ569-579, which behaved like control cells. These findings support a role of the GPIbβ intracellular domain in controlling the adhesive properties of the GPIb/V/IX complex through phosphorylation of GPIbβ Ser166 and point to the existence of cross-talk between the GPIbβ and GPIbα intracellular domains." @default.
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- W2148822857 date "2003-05-01" @default.
- W2148822857 modified "2023-10-18" @default.
- W2148822857 title "Role of the intracellular domains of GPIb in controlling the adhesive properties of the platelet GPIb/V/IX complex" @default.
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- W2148822857 doi "https://doi.org/10.1182/blood-2002-06-1847" @default.
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