Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

DRAK2

  • Jeniffer B. Hernandez
  • Ryan H. Newton
  • Brian M. Weist
  • Craig M. Walsh
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_85

Synonyms

Historical Background

 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 is a preview of subscription content, log in to check access.

Notes

Acknowledgments

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.

References

  1. Al-Qahtani A, Xu Z, Zan H, Walsh CM, Casali P. A role for DRAK2 in the germinal center reaction and the antibody response. Autoimmunity. 2008;41:341–52.PubMedPubMedCentralGoogle Scholar
  2. Bialik S, Kimchi A. The death-associated protein kinases: structure, function, and beyond. Annu Rev Biochem. 2006;75:189–210.Google Scholar
  3. Doherty GA, Byrne SM, Austin SC, Scully GM, Sadlier DM, Neilan TG, Kay EW, Murray FE, Fitzgerald DJ. Regulation of the apoptosis-inducing kinase DRAK2 by cyclooxygenase-2 in colorectal cancer. Br J Cancer. 2009;101:483–91.PubMedPubMedCentralGoogle Scholar
  4. 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
  5. 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
  6. 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
  7. Gatzka M, Newton RH, Walsh CM. Altered thymic selection and increased autoimmunity caused by ectopic expression of DRAK2 during T cell development. J Immunol. 2009b;183:285–97.PubMedPubMedCentralGoogle Scholar
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. McGargill MA, Wen BG, Walsh CM, Hedrick SM. A deficiency in Drak2 results in a T cell hypersensitivity and an unexpected resistance to autoimmunity. Immunity. 2004;21:781–91.PubMedPubMedCentralGoogle Scholar
  14. McGargill MA, Choy C, Wen BG, Hedrick SM. Drak2 regulates the survival of activated T cells and is required for organ-specific autoimmune disease. J Immunol. 2008;181:7593–605.PubMedPubMedCentralGoogle Scholar
  15. 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
  16. 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
  17. 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
  18. Ramos SJ, Hernandez JB, Gatzka M, Walsh CM. Enhanced T cell apoptosis within Drak2-deficient mice promotes resistance to autoimmunity. J Immunol. 2008;181:7606–16.PubMedPubMedCentralGoogle Scholar
  19. 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
  20. 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
  21. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, Hodge CL, Haase J, Janes J, Huss 3rd JW, Su AI. BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol. 2009;10:R130.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Jeniffer B. Hernandez
    • 1
  • Ryan H. Newton
    • 1
  • Brian M. Weist
    • 1
  • Craig M. Walsh
    • 1
  1. 1.Institute for Immunology and Department of Molecular Biology and BiochemistryUniversity of CaliforniaIrvineUSA