Dr. Ken Hsu (Assistant Professor of Chemistry and joint appointment in Pharmacology) and colleagues have just published an exciting paper in Nature Chemical Biology that establishes how diacylglycerol kinases (DGK) exhibit fatty acyl specificity. DGKs phosphorylate diacylglycerol to produce phosphatidic acid, both lipid second messengers with important roles in cancer, the immune response, and neural transmission.
The publication, “Reprogramming fatty acyl specificity of lipid kinases via C1 domain engineering” by Ware TB et al., re-defines the function of atypical C1 domains in diacylglycerol kinases as the determinants of fatty acyl chain substrate specificity. Swapping the C1 domains between various DGK isoforms changes the DGK substrate specificity both in vitro and in vivo. These findings advance our basic understanding of lipid signaling and provide promising targets for the future development of isoform-specific inhibitors.