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. 1996 Oct 1;93(20):11196–11201. doi: 10.1073/pnas.93.20.11196

A 104-kDa diacylglycerol kinase containing ankyrin-like repeats localizes in the cell nucleus.

K Goto 1, H Kondo 1
PMCID: PMC38307  PMID: 8855332

Abstract

The cDNA corresponding to a fourth species of diacylglycerol (DG) kinase (EC 2.7.1.107) was isolated from cDNA libraries of rat retina and brain. This cDNA encoded a 929-aa, 104-kDa polypeptide termed DGK-IV. DGK-IV was different from previously identified mammalian DG kinase species, DGK-I, DGK-II, and DGK-III, in that it contained no EF-hand motifs but did contain four ankyrin-like repeats at the carboxyl terminus. These structural features of DGK-IV closely resemble the recently cloned, eye-specific DG kinase of Drosophila that is encoded by the retinal degeneration A (rdgA) gene. However, DGK-IV was expressed primarily in the thymus and brain with relatively low expression in the eye and intestine. Furthermore, the primary structure of the DGK-IV included a nuclear targeting motif, and immunocytochemical analysis revealed DGK-IV to localize in the nucleus of COS-7 cells transfected with the epitope-tagged cDNA, suggesting an involvement of DGK-IV in intranuclear processes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abeliovich A., Chen C., Goda Y., Silva A. J., Stevens C. F., Tonegawa S. Modified hippocampal long-term potentiation in PKC gamma-mutant mice. Cell. 1993 Dec 31;75(7):1253–1262. doi: 10.1016/0092-8674(93)90613-u. [DOI] [PubMed] [Google Scholar]
  2. Abeliovich A., Paylor R., Chen C., Kim J. J., Wehner J. M., Tonegawa S. PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning. Cell. 1993 Dec 31;75(7):1263–1271. doi: 10.1016/0092-8674(93)90614-v. [DOI] [PubMed] [Google Scholar]
  3. Bailey C. H., Kandel E. R. Structural changes accompanying memory storage. Annu Rev Physiol. 1993;55:397–426. doi: 10.1146/annurev.ph.55.030193.002145. [DOI] [PubMed] [Google Scholar]
  4. Blank V., Kourilsky P., Israël A. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992 Apr;17(4):135–140. doi: 10.1016/0968-0004(92)90321-y. [DOI] [PubMed] [Google Scholar]
  5. Bocckino S. B., Wilson P. B., Exton J. H. Phosphatidate-dependent protein phosphorylation. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6210–6213. doi: 10.1073/pnas.88.14.6210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bunting M., Tang W., Zimmerman G. A., McIntyre T. M., Prescott S. M. Molecular cloning and characterization of a novel human diacylglycerol kinase zeta. J Biol Chem. 1996 Apr 26;271(17):10230–10236. [PubMed] [Google Scholar]
  7. Cockcroft S., Thomas G. M. Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J. 1992 Nov 15;288(Pt 1):1–14. doi: 10.1042/bj2880001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dingwall C., Laskey R. A. Nuclear targeting sequences--a consensus? Trends Biochem Sci. 1991 Dec;16(12):478–481. doi: 10.1016/0968-0004(91)90184-w. [DOI] [PubMed] [Google Scholar]
  10. Divecha N., Banfić H., Irvine R. F. The polyphosphoinositide cycle exists in the nuclei of Swiss 3T3 cells under the control of a receptor (for IGF-I) in the plasma membrane, and stimulation of the cycle increases nuclear diacylglycerol and apparently induces translocation of protein kinase C to the nucleus. EMBO J. 1991 Nov;10(11):3207–3214. doi: 10.1002/j.1460-2075.1991.tb04883.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Divecha N., Letcher A. J., Banfic H. H., Rhee S. G., Irvine R. F. Changes in the components of a nuclear inositide cycle during differentiation in murine erythroleukaemia cells. Biochem J. 1995 Nov 15;312(Pt 1):63–67. doi: 10.1042/bj3120063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goto K., Funayama M., Kondo H. Cloning and expression of a cytoskeleton-associated diacylglycerol kinase that is dominantly expressed in cerebellum. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13042–13046. doi: 10.1073/pnas.91.26.13042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goto K., Kondo H. Molecular cloning and expression of a 90-kDa diacylglycerol kinase that predominantly localizes in neurons. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7598–7602. doi: 10.1073/pnas.90.16.7598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goto K., Watanabe M., Kondo H., Yuasa H., Sakane F., Kanoh H. Gene cloning, sequence, expression and in situ localization of 80 kDa diacylglycerol kinase specific to oligodendrocyte of rat brain. Brain Res Mol Brain Res. 1992 Nov;16(1-2):75–87. doi: 10.1016/0169-328x(92)90196-i. [DOI] [PubMed] [Google Scholar]
  15. Huang F. L., Yoshida Y., Nakabayashi H., Young W. S., 3rd, Huang K. P. Immunocytochemical localization of protein kinase C isozymes in rat brain. J Neurosci. 1988 Dec;8(12):4734–4744. doi: 10.1523/JNEUROSCI.08-12-04734.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Inoue H., Yoshioka T., Hotta Y. Diacylglycerol kinase defect in a Drosophila retinal degeneration mutant rdgA. J Biol Chem. 1989 Apr 5;264(10):5996–6000. [PubMed] [Google Scholar]
  17. James G., Olson E. Deletion of the regulatory domain of protein kinase C alpha exposes regions in the hinge and catalytic domains that mediate nuclear targeting. J Cell Biol. 1992 Feb;116(4):863–874. doi: 10.1083/jcb.116.4.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kanoh H., Yamada K., Sakane F. Diacylglycerol kinase: a key modulator of signal transduction? Trends Biochem Sci. 1990 Feb;15(2):47–50. doi: 10.1016/0968-0004(90)90172-8. [DOI] [PubMed] [Google Scholar]
  19. Khan W. A., Blobe G. C., Richards A. L., Hannun Y. A. Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets. J Biol Chem. 1994 Apr 1;269(13):9729–9735. [PubMed] [Google Scholar]
  20. Malviya A. N., Block C. A bipartite nuclear targeting motif in protein kinase C? Trends Biochem Sci. 1992 May;17(5):176–176. doi: 10.1016/0968-0004(92)90259-c. [DOI] [PubMed] [Google Scholar]
  21. Martelli A. M., Gilmour R. S., Bertagnolo V., Neri L. M., Manzoli L., Cocco L. Nuclear localization and signalling activity of phosphoinositidase C beta in Swiss 3T3 cells. Nature. 1992 Jul 16;358(6383):242–245. doi: 10.1038/358242a0. [DOI] [PubMed] [Google Scholar]
  22. Masai I., Okazaki A., Hosoya T., Hotta Y. Drosophila retinal degeneration A gene encodes an eye-specific diacylglycerol kinase with cysteine-rich zinc-finger motifs and ankyrin repeats. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11157–11161. doi: 10.1073/pnas.90.23.11157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mochly-Rosen D., Khaner H., Lopez J. Identification of intracellular receptor proteins for activated protein kinase C. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3997–4000. doi: 10.1073/pnas.88.9.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nakagawa T., Goto K., Kondo H. Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase. J Biol Chem. 1996 May 17;271(20):12088–12094. doi: 10.1074/jbc.271.20.12088. [DOI] [PubMed] [Google Scholar]
  25. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
  26. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  27. Olson E. N., Burgess R., Staudinger J. Protein kinase C as a transducer of nuclear signals. Cell Growth Differ. 1993 Aug;4(8):699–705. [PubMed] [Google Scholar]
  28. Payrastre B., Nievers M., Boonstra J., Breton M., Verkleij A. J., Van Bergen en Henegouwen P. M. A differential location of phosphoinositide kinases, diacylglycerol kinase, and phospholipase C in the nuclear matrix. J Biol Chem. 1992 Mar 15;267(8):5078–5084. [PubMed] [Google Scholar]
  29. Rhee S. G., Suh P. G., Ryu S. H., Lee S. Y. Studies of inositol phospholipid-specific phospholipase C. Science. 1989 May 5;244(4904):546–550. doi: 10.1126/science.2541501. [DOI] [PubMed] [Google Scholar]
  30. Sakane F., Imai S., Kai M., Wada I., Kanoh H. Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases. J Biol Chem. 1996 Apr 5;271(14):8394–8401. doi: 10.1074/jbc.271.14.8394. [DOI] [PubMed] [Google Scholar]
  31. Stryer L. Cyclic GMP cascade of vision. Annu Rev Neurosci. 1986;9:87–119. doi: 10.1146/annurev.ne.09.030186.000511. [DOI] [PubMed] [Google Scholar]
  32. Suh P. G., Ryu S. H., Moon K. H., Suh H. W., Rhee S. G. Cloning and sequence of multiple forms of phospholipase C. Cell. 1988 Jul 15;54(2):161–169. doi: 10.1016/0092-8674(88)90548-x. [DOI] [PubMed] [Google Scholar]
  33. Tang W., Bunting M., Zimmerman G. A., McIntyre T. M., Prescott S. M. Molecular cloning of a novel human diacylglycerol kinase highly selective for arachidonate-containing substrates. J Biol Chem. 1996 Apr 26;271(17):10237–10241. [PubMed] [Google Scholar]
  34. Valdez B. C., Perlaky L., Henning D., Saijo Y., Chan P. K., Busch H. Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein B23. J Biol Chem. 1994 Sep 23;269(38):23776–23783. [PubMed] [Google Scholar]
  35. van Corven E. J., van Rijswijk A., Jalink K., van der Bend R. L., van Blitterswijk W. J., Moolenaar W. H. Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Dependence on acyl-chain length and inhibition by suramin. Biochem J. 1992 Jan 1;281(Pt 1):163–169. doi: 10.1042/bj2810163. [DOI] [PMC free article] [PubMed] [Google Scholar]

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