ROLE OF FIBRINOGEN ALPHA-CHAIN AND GAMMA-CHAIN SITES IN PLATELET-AGGREGATION
ROLE OF FIBRINOGEN ALPHA-CHAIN AND GAMMA-CHAIN SITES IN PLATELET-AGGREGATION
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DOI：
10.1073/pnas.89.22.10729
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发表时间：
1992-11-15
影响因子：
11.1
通讯作者：
DAVIE, EW
中科院分区：
文献类型：
--
作者：
FARRELL, DH;THIAGARAJAN, P;DAVIE, EW
纤维蛋白原（Fbg）通过与血小板糖蛋白IIb- iiia（整合素α (IIb) β 3）的相互作用介导血小板聚集。含有来自α链的氨基酸序列RGD（残基alpha95-97和残基alpha572-574）和来自Fbg γ链羧基末端的序列HHLGGAKQAGDV（残基gamma400-411）的肽段抑制了这些相互作用。为了确定这些序列在完整Fbg中的作用，在转染的BHK细胞中表达了重组人Fbg (rFbg)，在alpha97或alpha574位置具有RGD -> RGE替代的突变型rFbg，以及在HHLGGAKQAGDV序列中具有羧基末端中断的rFbg γ '-变体。纯化的Fbg和两种RGE突变的Fbg在血小板聚集试验中与血浆Fbg相似。相反，γ变异型Fbg在血小板聚集方面存在明显缺陷。这些数据支持了Fbg γ链羧基末端区域对于血小板聚集至关重要，而α链RGD序列对于血小板聚集既不是必要的也不是充分的。
Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein IIb-IIIa (integrin alpha(IIb)beta3). Peptides containing the amino acid sequence RGD derived from the alpha chain (residues alpha95-97 and residues alpha572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the gamma chain of Fbg (residues gamma400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD --> RGE substitution at either position alpha97 or alpha574, and a rFbg gamma'-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the gamma' variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the gamma chain of Fbg is essential for optimal platelet aggregation and that the alpha-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.