A proline-rich motif in the C terminus of Akt contributes to its localization in the immunological synapse
A proline-rich motif in the C terminus of Akt contributes to its localization in the immunological synapse
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DOI：
10.4049/jimmunol.172.9.5441
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Weiss, A
中科院分区：
文献类型：
--
作者：
Kane, LP;Mollenauer, MN;Weiss, A
Akt/蛋白激酶B家族的丝氨酸/苏氨酸激酶部分通过向质膜募集来调节，这是通过n端PH结构域与磷脂酰肌醇3-激酶产物磷酸肌醇3,4,5-三磷酸和磷酸肌醇3,4-二磷酸结合来完成的。我们研究了APC/Ag刺激前后小鼠T细胞克隆（D10）中Akt的定位，发现T细胞激活时Akt的质膜募集需要pleckstrin同源结构域，而激酶的C端将其细胞定位限制在T细胞/APC接触部位形成的免疫突触上。最近在该区域发现的富含脯氨酸的基序似乎对全长Akt的正确定位很重要。此外，该基序发生突变的一种Akt形式作为一种有效的显性负性结构体，可阻断T细胞的激活。因此，在T细胞激活的早期事件中，Akt的正确靶向涉及多种机制。
The serine/threonine kinases of the Akt/protein kinase B family are regulated in part by recruitment to the plasma membrane, which is accomplished by the binding of an N-terminal PH domain to the phosphatidylinositol 3-kinase products phosphoinositol 3,4,5-trisphosphate and phosphoinositol 3,4-bisphosphate. We have examined Akt localization in a murine T cell clone (D10) before and after stimulation by APC/Ag, and we found that whereas the pleckstrin homology domain is required for plasma membrane recruitment of Akt upon T cell activation, the C terminus of the kinase restricts its cellular localization to the immunologic synapse formed at the site of T cell/APC contact. A recently described proline-rich motif in this region appears to be important for proper localization of full-length Akt. Moreover, a form of Akt in which this motif was mutated acts as a potent dominant negative construct to block T cell activation. Therefore, multiple mechanisms are involved in the proper targeting of Akt during the early events of T cell activation.