Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity
Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity
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DOI：
10.1073/pnas.0611655104
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发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Strominger, Jack L.
中科院分区：
文献类型：
--
作者：
Chen, Xi;Trivedi, Prachi P.;Strominger, Jack L.
自然杀伤（NK）细胞是先天免疫系统的组分，其通过特异性NK活化受体/配体相互作用识别并杀死肿瘤或病毒感染的靶细胞。淋巴细胞功能相关抗原（LFA）-1及其配体ICAM-1也需要启动接合和肌动蛋白细胞骨架重塑。NK活化受体，其中许多在单个NK细胞上表达，向微管组织中心（MTOC）连同溶细胞颗粒向与靶细胞的突触的极化发出信号。在连接这些受体中的任何一种之后，Src家族激酶启动两种信号通路的激活，即磷酸肌醇-3激酶-> ERK 2和磷脂酶C γ-> JNK 1通路。两者都是MTOC和细胞溶解颗粒极化所必需的，这是杀死靶标的先决条件。CD 28、NKG 2D、NKp 30、NKp 46、NKG 2C/CD 94或2B 4的交联导致ERK 2和JNK 1的磷酸化，尽管它们使用不同的近端信号传导模块。因此，许多（如果不是全部）激活受体刺激这两条远端通路，而与所使用的近端信号模块无关。相比之下，CD 2、DNAM-1和β（1）-整联蛋白交联不激活任一途径;它们可能是共刺激分子或在突触中具有其他功能。
Natural killer (NK) cells are components of the innate immune system that recognize and kill tumor or virus-infected target cells through specific NK activating receptor/ligand interactions. Lymphocyte function-associated antigen (LFA)-1 and its ligand ICAM-1 are also required to initiate conjugation and actin cytoskeletal remodeling. The NK activating receptors, many of which are expressed on a single NK cell, signal the polarization of the microtubule organizing center (MTOC) together with cytolytic granules to the synapse with target cells. After ligation of any one of these receptors, Src family kinases initiate activation of two signal pathways, the phosphoinositide-3 kinase -> ERK2 and the phospholipase C gamma -> JNK1 pathways. Both are required for polarization of the MTOC and cytolytic granules, a prerequisite for killing the targets. Crosslinking of CD28, NKG2D, NKp30, NKp46, NKG2C/CD94, or 2B4 leads to the phosphorylation of both ERK2 and JNK1, although they use different proximal signaling modules. Thus, many, if not all, activating receptors stimulate these two distal pathways, independent of the proximal signaling module used. By contrast, CD2, DNAM-1, and beta(1)-integrin crosslinking do not activate either pathway; they may be costimulatory molecules or have another function in the synapse.