Abstract
Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR) signal by recruiting multiple effector molecules, such as RasGRP1, PKCθ, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms, α and ζ, in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation.
Highlights
Diacylglycerol (DAG) and phosphatidic acid (PA) are two key lipid second messengers that facilitate efficient receptor-mediated signaling in immune cells along with many other cells
The unexpected severe impairment of CD8 T cell-mediated immune responses to microbial infection in the absence of both DGKα and ζ underscores the importance of fine-tuning DAG levels and suggests potential negative feedback mechanisms triggered by deregulated DAG-mediated signaling
The drastic differences observed between DGKα and ζ double and single deficient CD8 T cells during immune responses beg for development of DGK isoform-specific inhibitors
Summary
Diacylglycerol (DAG) and phosphatidic acid (PA) are two key lipid second messengers that facilitate efficient receptor-mediated signaling in immune cells along with many other cells. Over the past few years, our understanding of the DGK family of enzymes in immune cells has been significantly advanced.
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