Kinase and Phosphatase Effector Pathways in T Cells

Abstract

Multiple interconnected effector pathways mediate the activation of T cells following recognition of cognate antigen. These kinase and phosphatase pathways link proximal T cell receptor (TCR) signaling to changes in gene expression and cell physiology. A key step in the TCR signaling cascade is the generation of the second messenger molecules inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium signaling, leading to activation of the transcription factor NFAT (nuclear factor of activated T cells), while DAG activates PKCθ and RasGRP1, which couple to the transcription factors NFκB (nuclear factor kappa B) and AP-1 (activator protein 1), respectively. The coordinated binding of these three transcription factors, NFAT, NFκB, and AP-1, to the promoter of the T cell survival cytokine interleukin-2 is a critical step in T cell activation. In this article, we cover the kinase and phosphatase pathways downstream of second messenger generation and discuss the role of these effectors in T cell development, activation, and differentiation.