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Publication : Dok1 and Dok2 proteins regulate natural killer cell development and function.

First Author  Celis-Gutierrez J Year  2014
Journal  EMBO J Volume  33
Issue  17 Pages  1928-40
PubMed ID  24963146 Mgi Jnum  J:214849
Mgi Id  MGI:5604075 Doi  10.15252/embj.201387404
Citation  Celis-Gutierrez J, et al. (2014) Dok1 and Dok2 proteins regulate natural killer cell development and function. EMBO J 33(17):1928-40
abstractText  Natural killer (NK) cells are involved in immune responses against tumors and microbes. NK-cell activation is regulated by intrinsic and extrinsic mechanisms that ensure NK tolerance and efficacy. Here, we show that the cytoplasmic signaling molecules Dok1 and Dok2 are tyrosine phosphorylated upon NK-cell activation. Overexpression of Dok proteins in human NK cells reduces cell activation induced by NK-cell-activating receptors. Dok1 and Dok2 gene ablation in mice induces an NK-cell maturation defect and leads to increased IFN-gamma production induced by activating receptors. Taken together, these results reveal that Dok1 and Dok2 proteins are involved in an intrinsic negative feedback loop downstream of NK-cell-activating receptors in mouse and human.
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