Cyclin G associated kinase interacts with interleukin 12 receptor beta2 and suppresses interleukin 12 induced IFN-gamma production

Interleukin 12 receptor beta1 (IL-12Rbeta1) and beta2 (IL-12Rbeta2) constitute the functional and high-affinity receptor complex for interleukin 12 (IL-12) and mediate important functions in activated T cells. In this study, we identified cyclin G associated kinase (GAK) as a new IL-12Rbeta2-interacting protein using yeast two-hybrid system and confirmed it by coimmunoprecipitation assays. Overexpression of GAK in activated T cells suppresses IL-12 induced IFN-gamma production but has no detectable effects on its proliferation, whereas knockdown of GAK by RNA interference (RNAi) increases IFN-gamma production. These results suggest that GAK associates with IL-12Rbeta2 and may play a role in regulating IL-12 signaling.