自然杀伤细胞活化信号的转导和效应

NK Cell Activating Receptors and Signalling Pathways

新近研究发现,NK细胞活化受体与靶细胞表面相应配体交联结合后,可通过以SLP-76和WASP为核心的信号传递复合体及PI3K途径发挥作用。SLP-76活化后,通过募集结合PLC-γ、Itk和Vav,形成SLP-76信号转导复合体;WASP活化后,通过募集结合Grb2、Vav、WIP、Arp2/3和Cdc42-GTP等,形成WASP信号转导复合体。上述2种信号转导复合体经Nck相连后,与浆膜上的LAT作用,进而活化其中的PLC-γ和Arp2/3复合体,最终导致转录因子NFAT活化、细胞因子(GM-CSF、IFN-γ等)分泌和肌动蛋白聚合。PI3K介导Rac/PAK/MEK/ERK途径,导致NK细胞脱颗粒,释放穿孔素和颗粒酶,诱导靶细胞凋亡。

The recent research about the model of activating signaling pathways in the natural killer (NK) cells allows us to shed new light on how NK cells function. Binding of activating receptors to its ligand(s) will lead to activation signals to proceed, resulting in activation of SLP-76, WASP and PI3K. Activated SLP-76 will recruit and bind many downstream molecules including PLC-γ, Itk and Vav, whereas activated WASP will recruit and bind Grb-2, Vav, WIP, Arp2/3 and Cdc42-GTP, among others. Nck, which binds to both SLP-76 and WASP, will transport the multimolecular signaling complex to cytomembrane where activated Arp2/3 and PLC-γ will partake in actin polymerization, cytoskeletal remodelling, NFAT gene transcription and cytokine secretion. Activation of PI3K will lead to granule polarization through Rac/PAK/MEK/ERK pathway.