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

Javier Celis-Gutierrez, Marilyn Boyron, Thierry Walzer, Pier Paolo Pandolfi, Stipan Jonjić, Daniel Olive, Marc Dalod, Eric Vivier, Jacques A Nunès

The EMBO journal 2014 Sep 01

filter terms:

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-γ 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. © 2014 The Authors.

Citation

Javier Celis-Gutierrez, Marilyn Boyron, Thierry Walzer, Pier Paolo Pandolfi, Stipan Jonjić, Daniel Olive, Marc Dalod, Eric Vivier, Jacques A Nunès. Dok1 and Dok2 proteins regulate natural killer cell development and function. The EMBO journal. 2014 Sep 01;33(17):1928-40