| 论文题目: | 14-3-3ζ-c-Src-integrin-β3 Complex Is Vital for Platelet Activation |
| 作者: | Shen C, Liu M, Xu R, Wang G, Li J, Chen P, Ma W, Mwangi J, Lu Q, Duan Z, Zhang Z, Dahmani FZ, Mackeigan D, Ni H, Lai R |
| 联系作者: | rlai@mail.kiz.ac.cn |
| 发表年度: | 2020 |
| DOI: | doi: 10.1182/blood.2019002314 |
| 摘要: | Several adaptor molecules bind to cytoplasmic tails of β-integrins and facilitate bidirectional signaling, which is critical in thrombosis and hemostasis. Interfering with integrin-adaptor interactions spatially or temporally to inhibit thrombosis without affecting hemostasis is an attractive strategy for the development of safe anti-thrombotics. Here we show for the first time that 14-3-3ζ-c-Src-integrin-β3 complex is formed during platelet activation. 14-3-3ζ-c-Src interaction is mediated by -pirlglalnfsvfyye- fragment (PE16) on 14-3-3ζ and SH2-domain on c-Src, while 14-3-3ζ-integrin β3 interaction is mediated by -eskvfylkmkgdyyrYL- fragment (EL17) on 14-3-3ζ and -keatstf- fragment (KF7) on β3 integrin cytoplasmic tail. EL17-motif inhibitor or KF7 peptide interferes with the formation of 14-3-3ζ-c-Src-integrin-β3 complex and selectively inhibits β3 outside-in signaling without affecting the integrin-fibrinogen interaction, which suppresses thrombosis without causing significant bleeding. This study characterizes a previously unidentified 14-3-3ζ-c-Src-integrin-β3 complex in platelets and provides a novel strategy for the development of safe and effective anti-thrombotic therapies |
| 刊物名称: | Blood |
| 论文出处: | https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2019002314/461127/14-3-3-c-Src-integrin-3-complex-is-vital-for?redirectedFrom=fulltext |
| 影响因子: | 16.601(2018年) |
