DRAK2 is a serine/threonine kinase of the death associate protein kinase (DAPK) family. Of this family, DRAK2 is most similar to DRAK1, and these two kinases may represent a unique family. DRAK1 and DRAK2 were originally identified using a polymerase chain reaction (PCR) screen to identify additional DAPK members, and was first thought to be primarily involved in promoting apoptosis (Sanjo et al. 1998). While humans have genes for both DRAK1 and DRAK2, mice lack a DRAK1 gene. Although ectopic expression of DRAK2 in cell lines does induce apoptosis (Sanjo et al. 1998; Matsumoto et al. 2001), it is unlikely that apoptotic induction is its key physiologic function since DRAK2-deficient mice demonstrate no obvious defects in apoptotic signaling (McGargill et al. 2004; Friedrich et al. 2005). Instead, DRAK2 has been shown to negatively regulate calcium signaling in primary T cells. Since its catalytic activity...
This work was supported by the National Institutes of Health (AI63419); the Arthritis National Research Foundation; the National Multiple Sclerosis Society; and the Juvenile Diabetes Research Foundation. R.H.N. was supported by National Institutes of Health Immunology Research Training Grant T32 AI-060573.
- Bialik S, Kimchi A. The death-associated protein kinases: structure, function, and beyond. Annu Rev Biochem. 2006;75:189–210.Google Scholar
- Friedrich ML, Wen BG, Bain G, Kee BL, Katayama C, Murre C, Hedrick SM, Walsh CM. DRAK2, a lymphoid-enriched DAP kinase, regulates the TCR activation threshold during thymocyte selection. Int Immunol. 2005;17:1379–90.Google Scholar
- Friedrich ML, Cui M, Hernandez JB, Weist BM, Andersen HM, Zhang X, Huang L, Walsh CM. Modulation of DRAK2 autophosphorylation by antigen receptor signaling in primary lymphocytes. J Biol Chem. 2007;282:4573–84.Google Scholar
- Gatzka M, Newton RH, Walsh CM. Negative regulation of TCR signaling in immunological tolerance: taming good and evil. Curr Immunol Rev J Immunol. 2009a;183(1):285–97.Google Scholar
- Kuwahara H, Nakamura N, Kanazawa H. Nuclear localization of the serine/threonine kinase DRAK2 is involved in UV-induced apoptosis. Biol Pharm Bull. 2006;29:225–33.Google Scholar
- Kuwahara H, Nishizaki M, Kanazawa H. Nuclear localization signal and phosphorylation of Serine350 specify intracellular localization of DRAK2. J Biochem. 2008;143:349–58.Google Scholar
- Mao J, Qiao X, Luo H, Wu J. Transgenic drak2 overexpression in mice leads to increased T cell apoptosis and compromised memory T cell development. J Biol Chem. 2006;281:12587–95.Google Scholar
- Mao J, Luo H, Han B, Bertrand R, Wu J. Drak2 is upstream of p70S6 kinase: its implication in cytokine-induced islet apoptosis, diabetes, and islet transplantation. J Immunol. 2009;182:4762–70.Google Scholar
- Matsumoto M, Miyake Y, Nagita M, Inoue H, Shitakubo D, Takemoto K, Ohtsuka C, Murakami H, Nakamura N, Kanazawa H. A serine/threonine kinase which causes apoptosis-like cell death interacts with a calcineurin B-like protein capable of binding Na(+)/H(+) exchanger. J Biochem. 2001;130:217–25.Google Scholar
- Newton RH, Leverrier S, Srikanth S, Gwack Y, Cahalan MD, Walsh CM. Protein kinase D orchestrates the activation of DRAK2 in response to TCR-induced Ca2+ influx and mitochondrial reactive oxygen generation. J Immunol. 2011;186(2):940–50.Google Scholar
- Pentcheva-Hoang T, Corse E, Allison JP. Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections. Immunol Rev. 2009;229:67–87.Google Scholar
- Ramos SJ, Hardison JL, Stiles LN, Lane TE, Walsh CM. Anti-viral effector T cell responses and trafficking are not dependent upon DRAK2 signaling following viral infection of the central nervous system. Autoimmunity. 2007;40:54–65.Google Scholar
- Sanjo H, Kawai T, Akira S. DRAKs, novel serine/threonine kinases related to death-associated protein kinase that trigger apoptosis. J Biol Chem. 1998;273:29066–71.Google Scholar
- Schaumburg CS, Gatzka M, Walsh CM, Lane TE. DRAK2 regulates memory T cell responses following murine coronavirus infection. Autoimmunity. 2007;40:483–8.Google Scholar