Diacylglycerol kinase alpha, from negative modulation of T cell activation to control of cancer progression

Like all other diacylglycerol kinase (DGK) family members, the best-characterized function of DGKα is that of a DAG receptor attenuator. This negative property of DGKα has been demonstrated clearly in T cell receptor (TCR) signaling. Studies in T lymphocytes demonstrate that attenuation of DGKα function is decisive in promoting the transition from an unresponsive/quiescent cell state, thus ensuring proliferation. DGKα might also exert this quiescence-induced function in other cell systems. Microarray studies point to DGKα as a p53 target gene, indicating that this enzyme participates in a cell program that protects against malignant transformation. Contrary to its negative regulation of DAG-mediated cell cycle progression, DGKα is required for growth factor receptor actions that result in cell proliferation, invasiveness and motility. DGKα participation in these mechanisms probably involves its phosphatidic acid (PA)-producing capacity. The dual role of DGKα in cell cycle progression suggests that this enzyme is part of a complex network that might be altered in cancerous states.