Blood:14-3-3ζ-c-Src-整合素-β3复合物对血小板激活至关重要!

2020-07-02 MedSci原创 MedSci原创

在血小板激活过程中,14-3-3ζ、c-Src和 integrin-β3形成14-3-3ζ-c-Src-integrin-β3复合物;该复合物干扰消除可在不引起出血的情况下抑制血栓形成。

几个适配器分子与β-整合素的胞内尾段结合,促进双向信号传导,这在血栓形成和止血中至关重要。在空间或时间上干扰整合素-适配器相互作用,以抑制血栓形成,且不影响止血是开发安全抗血栓形成剂的有吸引力的策略。

本研究首次报道在血小板激活过程中,会形成14-3-3ζ-c-Src-integrin(整合素)-β3复合物。14-3-3ζ-c-Src相互作用是由14-3-3ζ上的上清蛋白片段(PE16)和c-Src上的SH2结构域介导的,而14-3-3ζ-整合素-β3的相互作用是由14-3-3ζ上的eskvfylkmkgdyyrYL片段(EL17)和整合素-β3胞内尾段上的keatstf片段(KF7)介导的。

EL17模体抑制剂或FK7肽可干扰14-3-3ζ-c-Src-整合素-β3复合物的形成,选择性抑制β3的细胞外-内信号传导,且不影响整合素-纤维蛋白原的相互作用,从而抑制血栓形成而不引起明显出血。

本研究表征了血小板中既往未知的14-3-3ζ-c-Src-整合素-β3复合物,并为开发安全有效的抗血栓形成疗法提供了新的策略。

原始出处:

Chuanbin Shen,et al. 14-3-3ζ-c-Src-integrin-β3 complex is vital for platelet activation. Blood. June 25,2020.

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    2021-02-05 zhangxingru
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