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.
- Gatzka M, Newton RH, Walsh CM. Negative regulation of TCR signaling in immunological tolerance: taming good and evil. Curr Immunol Rev. J Immunol. 2009;183(1):285–97.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.PubMedCrossRefGoogle 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