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

ABSTRACT: 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-? 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.

SUBMITTER: Celis-Gutierrez J

PROVIDER: S-EPMC4195787 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Celis-Gutierrez Javier J Boyron Marilyn M Walzer Thierry T Pandolfi Pier Paolo PP Jonjić Stipan S Olive Daniel D Dalod Marc M Vivier Eric E Nunès Jacques A JA

The EMBO journal 20140624 17

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 d ...[more]

PMID: 24963146

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