Blocking ERK activity has a selective but critical impact on activating T cells

The mitogen activated kinases ERK1/2 are activated by antigen receptor engagement and control T cell differentiation. We have used mass spectrometry to explore how ERK1/2 control antigen receptor driven cell growth and proteome restructuring in CD8 T cells. Quantitative analysis of >8000 proteins provides new understanding of the highly selective role of ERK1/2 in controlling T cell protein systems. The data reveal that ERK signalling is not a dominant regulator of the metabolic and biosynthetic programs that drive T cell growth. Rather, the dominant function of ERK1/2 is to control the repertoire of transcription factors, cytokines and cytokine receptors expressed by activated T cells. This study provides a comprehensive map of how T cell phenotypes are selectively shaped by ERK1/2 and reveals that ERK1/2 controls the transcriptional reprogramming of activated T cells that is pivotal for T cell differentiation and acquisition of effector function.