MODULATION OF THE AFFINITY OF INTEGRIN-ALPHA-IIB-BETA-3 (GPIIB-IIIA) BY THE CYTOPLASMIC DOMAIN OF ALPHA-IIB
MODULATION OF THE AFFINITY OF INTEGRIN-ALPHA-IIB-BETA-3 (GPIIB-IIIA) BY THE CYTOPLASMIC DOMAIN OF ALPHA-IIB
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DOI：
10.1126/science.1948065
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发表时间：
1991-11-08
期刊：
影响因子：
56.9
通讯作者：
GINSBERG, MH
中科院分区：
文献类型：
--
作者：
OTOOLE, TE;MANDELMAN, D;GINSBERG, MH
细胞内信号传导改变了整合素在炎症、免疫反应、止血、血栓形成和视网膜发育中的粘附功能。通过截短α-IIb的胞质结构域，整联蛋白α-IIb-β-3对配体的亲和力增加。用来自整合素α-5的胞质结构域重建没有逆转增加的亲和力。因此，GPIIb-IIIa的α-亚基的胞质结构域控制配体结合亲和力，这表明通过整联蛋白的由内而外跨膜信号传导的机制。这些发现意味着人类存在迄今未被认识到的遗传性和获得性血栓性疾病。
Intracellular signaling alters integrin adhesive functions in inflammation, immune responses, hemostasis, thrombosis, and retinal development. By truncating the cytoplasmic domain of alpha-IIb, the affinity of integrin alpha-IIb-beta-3, for ligand was increased. Reconstitution with the cytoplasmic domain from integrin alpha-5 did not reverse the increased affinity. Thus, the cytoplasmic domain of the alpha-subunit of GPIIb-IIIa controls ligand binding affinity, which suggests mechanisms for inside-out transmembrane signaling through integrins. These findings imply the existence of hitherto unappreciated hereditary and acquired thrombotic disorders in humans.