Multiple Roles of the Stress Sensor GCN2 in Immune Cells

The serine/threonine-protein kinase general control nonderepressible 2 (GCN2) is a well-known stress sensor that responds to amino acid starvation and other stresses, making it critical to the maintenance of cellular and organismal homeostasis. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4(+) T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2 ' s functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.

Automated summary

The serine/threonine-protein kinase GCN2 is a stress sensor that responds to amino acid starvation and other stresses, playing a critical role in maintaining cellular and organismal homeostasis. Research spanning over 20 years has revealed the structure, inducers, signaling pathways, and functions of GCN2 in various processes and diseases. GCN2 is closely involved in the immune system, regulating macrophage polarization and CD4(+) T cell differentiation. Understanding GCN2's functions in the immune system will aid in developing therapies for immune-related diseases.