Formation of a WIP-, WASp-, actin-, and myosin IIA-containing multiprotein complex in activated NK cells and its alteration by KIR inhibitory signaling.
Formation of a WIP-, WASp-, actin-, and myosin IIA-containing multiprotein complex in activated NK cells and its alteration by KIR inhibitory signaling.
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DOI：
10.1083/jcb.200509076
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发表时间：
2006-04-10
影响因子：
7.8
通讯作者：
Strominger, Jack L
中科院分区：
文献类型：
--
作者：
Krzewski, Konrad;Chen, Xi;Orange, Jordan S;Strominger, Jack L
肿瘤自然杀伤（NK）细胞系YTS用于检查细胞溶解所需的细胞骨架重排。一种重约1.3 mD的多蛋白复合物，由WASP相互作用蛋白（WASP）、Wiskott-Aldrich综合征蛋白（WASp）、肌动蛋白和肌球蛋白IIA组成，在NK细胞活化过程中形成。诱导抑制信号后，招募肌动蛋白和肌球蛋白IIA组成的WIP-WASp复合物大大减少。肌动蛋白和肌球蛋白IIA都被招募到WASp不存在的情况下。这种募集与PKCθ介导的PKC β磷酸化增加相关。此外，通过干扰RNA干扰破坏cRNA表达阻止了这种蛋白复合物的形成，并导致几乎完全抑制细胞毒活性。因此，多蛋白复合物对于NK细胞功能是重要的，杀伤细胞免疫球蛋白样受体抑制性信号传导影响参与细胞骨架重排的蛋白质，并且在复合物的形成和NK细胞活性的调节中，CD 14起核心作用。
The tumor natural killer (NK) cell line YTS was used to examine the cytoskeletal rearrangements required for cytolysis. A multiprotein complex weighing ∼1.3 mD and consisting of WASp-interacting protein (WIP), Wiskott-Aldrich syndrome protein (WASp), actin, and myosin IIA that formed during NK cell activation was identified. After induction of an inhibitory signal, the recruitment of actin and myosin IIA to a constitutive WIP–WASp complex was greatly decreased. Both actin and myosin IIA were recruited to WIP in the absence of WASp. This recruitment correlated with increased WIP phosphorylation, which was mediated by PKCθ. Furthermore, the disruption of WIP expression by WIP RNA interference prevented the formation of this protein complex and led to almost complete inhibition of cytotoxic activity. Thus, the multiprotein complex is important for NK cell function, killer cell immunoglobulin-like receptor inhibitory signaling affects proteins involved in cytoskeletal rearrangements, and WIP plays a central role in the formation of the complex and in the regulation of NK cell activity.