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Gene Review

DGKZ  -  diacylglycerol kinase, zeta

Homo sapiens

Synonyms: DAG kinase zeta, DAGK5, DAGK6, DGK-ZETA, DGK-zeta, ...
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Disease relevance of DGKZ


Psychiatry related information on DGKZ


High impact information on DGKZ

  • The nuclear-localization signal of DGK-zeta is located in a region that is homologous to the phosphorylation-site domain of the MARCKS protein [4].
  • Reducing nuclear diacylglycerol levels by conditional expression of DGK-zeta attenuates cell growth [4].
  • When stimulated in anergy-producing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleukin 2 [5].
  • Phosphorylation of this motif significantly attenuated coimmunoprecipitation of DGKzeta and PKCalpha and abolished their colocalization in cells, indicating that it negatively regulates binding [6].
  • We also show that DGKzeta directly interacts with PKCalpha in a signaling complex and that the binding site in DGKzeta is located within the catalytic domain [6].

Biological context of DGKZ


Anatomical context of DGKZ


Associations of DGKZ with chemical compounds


Physical interactions of DGKZ

  • DGK zeta also coimmunoprecipitated with PKC alpha, suggesting that they reside in a regulated signaling complex [7].

Co-localisations of DGKZ

  • We also observed that DGKzeta co-immunoprecipitated and co-localized with PIP5KIalpha, suggesting that they reside in a regulated signaling complex [15].

Regulatory relationships of DGKZ

  • Furthermore, activation of PKC alpha by phorbol 12-myristate 13-acetate inhibited the activity of wild-type DGK zeta, but not DGK zeta S/D, in human embryonic kidney 293 cells [7].
  • Collectively, our results suggest that gamma 1-syntrophin participates in regulating the subcellular localization of DGK-zeta to ensure correct termination of diacylglycerol signaling [11].
  • Down-regulation of endogenous DGKzeta by small interfering RNA in HEK293 cells diminished serum-induced p70S6K phosphorylation, highlighting the role of this isoform in the mTOR pathway [16].
  • Here we show that expression of DGKzeta significantly enhances PIP5KIalpha activity in thrombin-stimulated HEK293 cells, and DGK activity is required for this stimulation [15].

Other interactions of DGKZ


Analytical, diagnostic and therapeutic context of DGKZ


  1. Diacylglycerol kinase zeta in hypothalamus interacts with long form leptin receptor. Relation to dietary fat and body weight regulation. Liu, Z., Chang, G.Q., Leibowitz, S.F. J. Biol. Chem. (2001) [Pubmed]
  2. Diacylglycerol kinase zeta is involved in the process of cerebral infarction. Nakano, T., Hozumi, Y., Ali, H., Saino-Saito, S., Kamii, H., Sato, S., Kayama, T., Watanabe, M., Kondo, H., Goto, K. Eur. J. Neurosci. (2006) [Pubmed]
  3. An N-terminal fragment of ProSAAS (a granin-like neuroendocrine peptide precursor) is associated with tau inclusions in Pick's disease. Kikuchi, K., Arawaka, S., Koyama, S., Kimura, H., Ren, C.H., Wada, M., Kawanami, T., Kurita, K., Daimon, M., Kawakatsu, S., Kadoya, T., Goto, K., Kato, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  4. Protein kinase C regulates the nuclear localization of diacylglycerol kinase-zeta. Topham, M.K., Bunting, M., Zimmerman, G.A., McIntyre, T.M., Blackshear, P.J., Prescott, S.M. Nature (1998) [Pubmed]
  5. Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Olenchock, B.A., Guo, R., Carpenter, J.H., Jordan, M., Topham, M.K., Koretzky, G.A., Zhong, X.P. Nat. Immunol. (2006) [Pubmed]
  6. Association of diacylglycerol kinase zeta with protein kinase C alpha: spatial regulation of diacylglycerol signaling. Luo, B., Prescott, S.M., Topham, M.K. J. Cell Biol. (2003) [Pubmed]
  7. Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta. Luo, B., Prescott, S.M., Topham, M.K. J. Biol. Chem. (2003) [Pubmed]
  8. Alternative splicing of the human diacylglycerol kinase zeta gene in muscle. Ding, L., Bunting, M., Topham, M.K., McIntyre, T.M., Zimmerman, G.A., Prescott, S.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Dynamics of diacylglycerol kinase zeta translocation in living T-cells. Study of the structural domain requirements for translocation and activity. Santos, T., Carrasco, S., Jones, D.R., Mérida, I., Eguinoa, A. J. Biol. Chem. (2002) [Pubmed]
  10. Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism. Topham, M.K., Prescott, S.M. J. Cell Biol. (2001) [Pubmed]
  11. Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions. Hogan, A., Shepherd, L., Chabot, J., Quenneville, S., Prescott, S.M., Topham, M.K., Gee, S.H. J. Biol. Chem. (2001) [Pubmed]
  12. Gonadotropin-releasing hormone-induced activation of diacylglycerol kinase-zeta and its association with active c-src. Davidson, L., Pawson, A.J., De Maturana, R.L., Freestone, S.H., Barran, P., Millar, R.P., Maudsley, S. J. Biol. Chem. (2004) [Pubmed]
  13. Molecular cloning and characterization of a novel human diacylglycerol kinase zeta. Bunting, M., Tang, W., Zimmerman, G.A., McIntyre, T.M., Prescott, S.M. J. Biol. Chem. (1996) [Pubmed]
  14. Regulation of T cell receptor-induced activation of the Ras-ERK pathway by diacylglycerol kinase zeta. Zhong, X.P., Hainey, E.A., Olenchock, B.A., Zhao, H., Topham, M.K., Koretzky, G.A. J. Biol. Chem. (2002) [Pubmed]
  15. Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. Luo, B., Prescott, S.M., Topham, M.K. Cell. Signal. (2004) [Pubmed]
  16. Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid. Avila-Flores, A., Santos, T., Rincón, E., Mérida, I. J. Biol. Chem. (2005) [Pubmed]
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