The sorbin homology domain: A motif for the targeting of proteins to lipid rafts
The sorbin homology domain: A motif for the targeting of proteins to lipid rafts
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DOI：
10.1073/pnas.151252898
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发表时间：
2001-07-31
影响因子：
11.1
通讯作者：
Saltiel, AR
中科院分区：
文献类型：
--
作者：
Kimura, A;Baumann, CA;Saltiel, AR
在Cbl磷酸化时，c-Cbl相关蛋白（CAP）/Cbl复合物从胰岛素受体解离并易位至脂筏膜部分，与flotillin形成三元复合物。CAP基因的缺失分析确定了一个115个氨基酸的区域负责flotillin结合。该区域与肽sorbin同源，并被称为sorbin同源（SoHo）结构域。该结构域存在于另外两种蛋白质中，vinexin和ArgBP 2。Vinexin也与flotillin相互作用，并且其SoHo结构域的缺失类似地阻断flotillin结合。过表达的CAP突变体，其中SoHo结构域已被删除（CAP SoHo）防止易位的Cbl脂筏，随后阻止招聘的CrkII和C3 G。此外，CAP Delta SoHo的过表达阻止了胰岛素对葡萄糖转运和GLUT 4易位的刺激。这些结果提示了信号蛋白定位于脂筏的机制，其介导了关键信号转导途径的区室化。
On phosphorylation of Cbl, the c-Cbl-associated protein (CAP)/Cbl complex dissociates from the insulin receptor and translocates to a lipid raft membrane fraction to form a ternary complex with flotillin. Deletion analyses of the CAP gene identified a 115-aa region responsible for flotillin binding. This region is homologous to the peptide sorbin and is referred to as the sorbin homology (SoHo) domain. This domain is present in two other proteins, vinexin and ArgBP2. Vinexin also interacted with flotillin, and deletion of its SoHo domain similarly blocked flotillin binding. The overexpression of a CAP mutant in which the SoHo domain had been deleted (CAP SoHo) prevented the translocation of Cbl to lipid rafts and subsequently blocked the recruitment of CrkII and C3G. Moreover, overexpression of CAP Delta SoHo prevented the stimulation of glucose transport and GLUT4 translocation by insulin. These results suggest a mechanism for Localization of signaling proteins to the lipid raft that mediates the compartmentalization of crucial signal transduction pathways.