Myr-RKEFAK肽选择性调控血小板外向内信号转导相关功能  

Myr-RKEFAK Peptide Selectively Regulates Outside-in Signaling Transduction-related Functions in Human Platelets

作　　者：龙章彪[1] 黄建松[1] 施小凤[1] 杨纪春[1] 阮铮[1] 肖兵[1] 奚晓东[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海血液学研究所医学基因组学国家重点实验室,上海200025

出　　处：《中国实验血液学杂志》2015年第3期761-767,共7页Journal of Experimental Hematology

基　　金：国家重点基础研究发展计划(973)项目(2013CB966800);国家自然科学基金(81270594)

摘　　要：目的:研究踝蛋白杆部整合素结合位点2与整合素β3相互作用对于血小板信号转导的影响。方法:设计合成模拟整合素β3胞浆近膜端α螺旋上6个氨基酸序列(R724KEFAK729)的寡肽,并通过十四烷酰化修饰以使其具有穿细胞膜性(myr-RKEFAK肽)。观察myr-RKEFAK肽对经典血小板外向内信号转导事件(固相纤维蛋白原上的稳定黏附和伸展、二相聚集、纤维蛋白凝块回缩),以及内向外信号转导事件(一相聚集、游离纤维蛋白原的结合)的影响。结果:myr-RKEFAK肽可以浓度依赖性地抑制血小板固相化纤维蛋白原上稳定黏附和伸展、二相聚集以及纤维蛋白凝块回缩等外向内信号转导功能;但不影响游离纤维蛋白原结合和一相聚集等内向外信号转导功能。结论:穿膜肽myr-RKEFAK对血小板的外向内信号转导相应功能产生抑制,但不影响血小板内向外信号转导相关功能。Objective： To study the effect of interaction of the talin rod domain integrin binding site 2 with integrin β3 on platelet signal transduction. Methods： A peptide that mimics the membrane proximal et helix 6 residues R724 KEFAK729 of the integrin β3 cytoplasmic tails was designed and synthesized, to which the myristoylation was covalently linked to the N-terminal of the peptide enabling membrane penetration. The effects of myr-RKEFAK peptide on the typical platelet outside-in signaling ovent （ stable adhesion and spreading on immobilized fibrinogen, aggregation, fibrin clot retraction） and inside-out signaling events （soluble fibrinogen binding） were tested. Results： myr-RKEFAK peptide dose-dependently inhibited platelet stable adhesion and spreading on immobilized fibrinogen, irreversible aggregation, as well as fibrin clot retraction, but not soluble fibrinogen binding and reversible phase of platelet aggregation. Conclusion： The cell-penetrating peptide myr-RKEFAK causes an inhibitory effect on integrin 133 outside-in signaling-regulated platelets functions, but did not affect inside-out signaling-regulated platelets functions.

关 键 词：整合素Β3 踝蛋白杆部 整合素结合位点2 myr-RKEFAK肽 血小板信号转导 

分 类 号：R331.143[医药卫生—人体生理学]