Abstract
Some sensors of extracellular signaling molecules such as Notch and sterol response element binding protein (SREBP) receive ligand-induced intra-membrane proteolysis followed by nuclear translocation of their cytoplasmic domains to regulate gene expression programs in the nucleus. It has not been extensively examined whether ligand-induced intra-membrane proteolysis of type I cytokine receptors and nuclear translocation of cytoplasmic domains occur. Here, by using a sensitive reporter system, we examined this possibility for the interleukin-2 (IL-2) receptor (IL-2R) beta-chain (IL-2R beta) and the IL-15 receptor (IL-15R) alpha-chain (IL-15R alpha). Flowcytometric analysis revealed that ligand stimulation does not induce nuclear translocation of their cytoplasmic domains. In addition, overexpression of the cytoplasmic domain of the common cytokine receptor gamma-chain (gamma c) in an IL-2R-reconstituted Ba/F3-derived cell line did not affect any biological responses including cell survival, disproving potential roles of the cleaved cytoplasmic domain of gamma c as a signal transducer. Collectively, these results indicated that potential nuclear function of cleaved type I cytokine receptor subunits is not plausible.