Diacylglycerol kinase alpha, from negative modulation of T cell activation to control of cancer progression |
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Authors: | Isabel M rida, Antonia Avila-Flores, Job Garcí a, Ernesto Merino, Marí a Almena,Pedro Torres-Ayuso |
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Affiliation: | aDepartment of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin, 3, Campus de Cantoblanco, E-28049 Madrid, Spain |
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Abstract: | 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. |
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Keywords: | Diacylglycerol kinase, DGK Sphingosine kinase, SPK Ceramide kinase, CERK Vascular endothelial growth factor, VEGF Hepatocyte growth factor, HGF Epidermal growth factor, EGF Protein kinase C, PKC Protein kinase D, PKD Peroxisome proliferator-activated receptor-γ, PPARγ Nitric oxide, NO Ras guanyl nucleotide-releasing protein, RasGRP1 T cell receptor, TCR Mammalian target of rapamycin, mTOR Phosphatidylinositol 3 kinase, PI3K Hypoxia-inducible factor type 1α, HIF-1α Anaplastic large cell lymphoma, ALCL Nucleophosmin-anaplastic lymphoma kinase, NPM-ALK |
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