Nola eragiten du 2-Interleukinak T-zelulen nukleoko proteinen fosforilazio mailan?

Abstract

Immunotherapy aims to fight against diseases such as cancer by boosting the immune system of the patients. For that purpose, patients are usually treated with a molecule called interleukin-2 (IL-2), which plays a pivotal role in modulating the immune system and specially in promoting the proliferation of T-cells. Unfortunately, administration of IL-2 is usually accompanied by severe side effects that must be overcome. To achieve this, it is mandatory to understand in detail the molecular effects triggered in T-cells upon IL-2 stimulation. It is known that signaling events initiated at the cell surface are mainly transduced inside the cell through transient phosphorylations occurring in distinct proteins. For that reason our previous study focused on dissecting the signaling pathways triggered in IL-2-treated T lymphocytes by studying the proteins that become tyrosine phosphorylation upon the stimuli using mass spectrometry. In the present study, we aimed to unveil how IL-2 modulates the phosphorylation status of the nuclear proteins in T-cells, which ultimately will affect gene expression and the fate of the cell. Following a quantitative mass spectrometry-based approach a total of 8521 phosphorylated aminoacids were quantified at least in one of the 3 replicas of the same experiment that were performed. Whereas the phosphorylation levels of most phosphosites remained unaffected in IL-2-treated and untreated T-cells, the phosphorylation status of 391 phosphosites was found to be dramatically modulated upon IL-2 stimulation. Further investigation will unveil the biological significance of such findings.