Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization.
Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization.
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DOI：
10.1016/j.devcel.2013.01.007
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发表时间：
2013-02-25
影响因子：
11.8
通讯作者：
Grinstein, Sergio
中科院分区：
文献类型：
--
作者：
Heit, Bryan;Kim, Hani;Cosio, Gabriela;Castano, Diana;Collins, Richard;Lowell, Clifford A.;Kain, Kevin C.;Trimble, William S.;Grinstein, Sergio
CD 36是一种多功能受体，已知在动脉粥样硬化的发展、疟疾的发病机制和凋亡细胞的去除中发挥核心作用。值得注意的是，CD 36的短的胞内暴露区域缺乏可识别的基序，这阻碍了其信号传导模式的阐明。使用磷蛋白分离、质谱、超分辨率成像和基因沉默的组合，我们已经确定受体通过由CD 36、β1和/或β2整联蛋白以及四跨膜蛋白CD 9和/或CD 81组成的异聚复合物诱导配体内化。该受体复合物用于将CD 36连接至具有免疫受体酪氨酸活化基序的衔接子FcRγ。通过与FcRγ偶联，CD 36能够接合Src家族激酶和Syk，这进而驱动CD 36及其结合配体的内化。
CD36 is a versatile receptor known to play a central role in the development of atherosclerosis, the pathogenesis of malaria, and in the removal of apoptotic cells. Remarkably, the short cytosolically-exposed regions of CD36 lack identifiable motifs, which has hampered elucidation of its mode of signaling. Using a combination of phosphoprotein isolation, mass spectrometry, super-resolution imaging and gene silencing we have determined that the receptor induces ligand internalization through a heteromeric complex consisting of CD36, β1 and/or β2 integrins, and the tetraspanins CD9 and/or CD81. This receptor complex serves to link CD36 to the adaptor FcRγ, which bears an immunoreceptor tyrosine activation motif. By coupling to FcRγ, CD36 is able to engage Src-family kinases and Syk, which in turn drives the internalization of CD36 and its bound ligands.
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影响因子：
64.8
作者：
Hoebe, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
CD36介导了对β-淀粉样蛋白的先天宿主反应。
影响因子：
15.3
作者：
El Khoury, JB;Moore, KJ;Means, TK;Leung, J;Terada, K;Toft, M;Freeman, MW;Luster, AD
通讯作者：
Luster, AD
影响因子：
6
作者：
Coraci, IS;Husemann, J;El Khoury, JB
通讯作者：
El Khoury, JB
影响因子：
11.4
作者：
Barda-Saad, Mira;Shirasu, Naoto;Samelson, Lawrence E.
通讯作者：
Samelson, Lawrence E.
影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL