Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression (original) (raw)

Abstract

Phosphorylation of CREB (cyclic AMP [cAMP]- response element [CRE]-binding protein) by cAMP-dependent protein kinase (PKA) leads to the activation of many promoters containing CREs. In neurons and other cell types, CREB phosphorylation and activation of CRE-containing promoters can occur in response to elevated intracellular Ca2+. In cultured cells that normally lack this Ca2+ responsiveness, we confer Ca(2+)-mediated activation of a CRE-containing promoter by introducing an expression vector for Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV). Activation could also be mediated directly by a constitutively active form of CaMKIV which is Ca2+ independent. The CaMKIV-mediated gene induction requires the activity of CREB/ATF family members but is independent of PKA activity. In contrast, transient expression of either a constitutively active or wild-type Ca2+/calmodulin-dependent protein kinase type II (CaMKII) fails to mediate the transactivation of the same CRE-containing reporter gene. Examination of the subcellular distribution of transiently expressed CaMKIV and CaMKII reveals that only CaMKIV enters the nucleus. Our results demonstrate that CaMKIV, which is expressed in neuronal, reproductive, and lymphoid tissues, may act as a mediator of Ca(2+)-dependent gene induction.

6107

Images in this article

Selected References

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

  1. Bading H., Ginty D. D., Greenberg M. E. Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science. 1993 Apr 9;260(5105):181–186. doi: 10.1126/science.8097060. [DOI] [PubMed] [Google Scholar]
  2. Bentley J. K., Beavo J. A. Regulation and function of cyclic nucleotides. Curr Opin Cell Biol. 1992 Apr;4(2):233–240. doi: 10.1016/0955-0674(92)90038-e. [DOI] [PubMed] [Google Scholar]
  3. Boutillier A. L., Barthel F., Roberts J. L., Loeffler J. P. Beta-adrenergic stimulation of cFOS via protein kinase A is mediated by cAMP regulatory element binding protein (CREB)-dependent and tissue-specific CREB-independent mechanisms in corticotrope cells. J Biol Chem. 1992 Nov 25;267(33):23520–23526. [PubMed] [Google Scholar]
  4. Choi E. J., Xia Z., Villacres E. C., Storm D. R. The regulatory diversity of the mammalian adenylyl cyclases. Curr Opin Cell Biol. 1993 Apr;5(2):269–273. doi: 10.1016/0955-0674(93)90115-7. [DOI] [PubMed] [Google Scholar]
  5. Clegg C. H., Correll L. A., Cadd G. G., McKnight G. S. Inhibition of intracellular cAMP-dependent protein kinase using mutant genes of the regulatory type I subunit. J Biol Chem. 1987 Sep 25;262(27):13111–13119. [PubMed] [Google Scholar]
  6. Cohen P. The structure and regulation of protein phosphatases. Annu Rev Biochem. 1989;58:453–508. doi: 10.1146/annurev.bi.58.070189.002321. [DOI] [PubMed] [Google Scholar]
  7. Correll L. A., Woodford T. A., Corbin J. D., Mellon P. L., McKnight G. S. Functional characterization of cAMP-binding mutations in type I protein kinase. J Biol Chem. 1989 Oct 5;264(28):16672–16678. [PubMed] [Google Scholar]
  8. Cruzalegui F. H., Kapiloff M. S., Morfin J. P., Kemp B. E., Rosenfeld M. G., Means A. R. Regulation of intrasteric inhibition of the multifunctional calcium/calmodulin-dependent protein kinase. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12127–12131. doi: 10.1073/pnas.89.24.12127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cruzalegui F. H., Means A. R. Biochemical characterization of the multifunctional Ca2+/calmodulin-dependent protein kinase type IV expressed in insect cells. J Biol Chem. 1993 Dec 15;268(35):26171–26178. [PubMed] [Google Scholar]
  10. Dash P. K., Karl K. A., Colicos M. A., Prywes R., Kandel E. R. cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5061–5065. doi: 10.1073/pnas.88.11.5061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edlund T., Walker M. D., Barr P. J., Rutter W. J. Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements. Science. 1985 Nov 22;230(4728):912–916. doi: 10.1126/science.3904002. [DOI] [PubMed] [Google Scholar]
  12. Enslen H., Sun P., Brickey D., Soderling S. H., Klamo E., Soderling T. R. Characterization of Ca2+/calmodulin-dependent protein kinase IV. Role in transcriptional regulation. J Biol Chem. 1994 Jun 3;269(22):15520–15527. [PubMed] [Google Scholar]
  13. Frangakis M. V., Chatila T., Wood E. R., Sahyoun N. Expression of a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, in rat thymus. J Biol Chem. 1991 Sep 15;266(26):17592–17596. [PubMed] [Google Scholar]
  14. Frangakis M. V., Ohmstede C. A., Sahyoun N. A brain-specific Ca2+/calmodulin-dependent protein kinase (CaM kinase-Gr) is regulated by autophosphorylation. Relevance to neuronal Ca2+ signaling. J Biol Chem. 1991 Jun 15;266(17):11309–11316. [PubMed] [Google Scholar]
  15. Ginty D. D., Glowacka D., Bader D. S., Hidaka H., Wagner J. A. Induction of immediate early genes by Ca2+ influx requires cAMP-dependent protein kinase in PC12 cells. J Biol Chem. 1991 Sep 15;266(26):17454–17458. [PubMed] [Google Scholar]
  16. Gonzalez G. A., Montminy M. R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 1989 Nov 17;59(4):675–680. doi: 10.1016/0092-8674(89)90013-5. [DOI] [PubMed] [Google Scholar]
  17. Griffith L. C., Schulman H. The multifunctional Ca2+/calmodulin-dependent protein kinase mediates Ca2+-dependent phosphorylation of tyrosine hydroxylase. J Biol Chem. 1988 Jul 5;263(19):9542–9549. [PubMed] [Google Scholar]
  18. Hanson P. I., Schulman H. Neuronal Ca2+/calmodulin-dependent protein kinases. Annu Rev Biochem. 1992;61:559–601. doi: 10.1146/annurev.bi.61.070192.003015. [DOI] [PubMed] [Google Scholar]
  19. Jensen K. F., Ohmstede C. A., Fisher R. S., Sahyoun N. Nuclear and axonal localization of Ca2+/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2850–2853. doi: 10.1073/pnas.88.7.2850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones D. A., Glod J., Wilson-Shaw D., Hahn W. E., Sikela J. M. cDNA sequence and differential expression of the mouse Ca2+/calmodulin-dependent protein kinase IV gene. FEBS Lett. 1991 Sep 2;289(1):105–109. doi: 10.1016/0014-5793(91)80919-t. [DOI] [PubMed] [Google Scholar]
  21. Kameshita I., Fujisawa H. Autophosphorylation of calmodulin-dependent protein kinase IV from rat cerebral cortex. J Biochem. 1993 May;113(5):583–590. doi: 10.1093/oxfordjournals.jbchem.a124087. [DOI] [PubMed] [Google Scholar]
  22. Kameshita I., Fujisawa H. Phosphorylation and functional modification of calmodulin-dependent protein kinase IV by cAMP-dependent protein kinase. Biochem Biophys Res Commun. 1991 Oct 15;180(1):191–196. doi: 10.1016/s0006-291x(05)81275-6. [DOI] [PubMed] [Google Scholar]
  23. Kanaseki T., Ikeuchi Y., Sugiura H., Yamauchi T. Structural features of Ca2+/calmodulin-dependent protein kinase II revealed by electron microscopy. J Cell Biol. 1991 Nov;115(4):1049–1060. doi: 10.1083/jcb.115.4.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Low M. J., Hammer R. E., Goodman R. H., Habener J. F., Palmiter R. D., Brinster R. L. Tissue-specific posttranslational processing of pre-prosomatostatin encoded by a metallothionein-somatostatin fusion gene in transgenic mice. Cell. 1985 May;41(1):211–219. doi: 10.1016/0092-8674(85)90075-3. [DOI] [PubMed] [Google Scholar]
  25. McDonald O. B., Merrill B. M., Bland M. M., Taylor L. C., Sahyoun N. Site and consequences of the autophosphorylation of Ca2+/calmodulin-dependent protein kinase type "Gr". J Biol Chem. 1993 May 15;268(14):10054–10059. [PubMed] [Google Scholar]
  26. Means A. R., Cruzalegui F., LeMagueresse B., Needleman D. S., Slaughter G. R., Ono T. A novel Ca2+/calmodulin-dependent protein kinase and a male germ cell-specific calmodulin-binding protein are derived from the same gene. Mol Cell Biol. 1991 Aug;11(8):3960–3971. doi: 10.1128/mcb.11.8.3960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mellon P. L., Clegg C. H., Correll L. A., McKnight G. S. Regulation of transcription by cyclic AMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4887–4891. doi: 10.1073/pnas.86.13.4887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miyano O., Kameshita I., Fujisawa H. Purification and characterization of a brain-specific multifunctional calmodulin-dependent protein kinase from rat cerebellum. J Biol Chem. 1992 Jan 15;267(2):1198–1203. [PubMed] [Google Scholar]
  29. Mochizuki H., Ito T., Hidaka H. Purification and characterization of Ca2+/calmodulin-dependent protein kinase V from rat cerebrum. J Biol Chem. 1993 Apr 25;268(12):9143–9147. [PubMed] [Google Scholar]
  30. Ohmstede C. A., Jensen K. F., Sahyoun N. E. Ca2+/calmodulin-dependent protein kinase enriched in cerebellar granule cells. Identification of a novel neuronal calmodulin-dependent protein kinase. J Biol Chem. 1989 Apr 5;264(10):5866–5875. [PubMed] [Google Scholar]
  31. Okuno S., Fujisawa H. Requirement of brain extract for the activity of brain calmodulin-dependent protein kinase IV expressed in Escherichia coli. J Biochem. 1993 Aug;114(2):167–170. doi: 10.1093/oxfordjournals.jbchem.a124149. [DOI] [PubMed] [Google Scholar]
  32. Orellana S. A., McKnight G. S. Mutations in the catalytic subunit of cAMP-dependent protein kinase result in unregulated biological activity. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4726–4730. doi: 10.1073/pnas.89.10.4726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Orellana S. A., McKnight G. S. The S49 Kin- cell line transcribes and translates a functional mRNA coding for the catalytic subunit of cAMP-dependent protein kinase. J Biol Chem. 1990 Feb 25;265(6):3048–3053. [PubMed] [Google Scholar]
  34. Otten A. D., McKnight G. S. Overexpression of the type II regulatory subunit of the cAMP-dependent protein kinase eliminates the type I holoenzyme in mouse cells. J Biol Chem. 1989 Dec 5;264(34):20255–20260. [PubMed] [Google Scholar]
  35. Ouimet C. C., McGuinness T. L., Greengard P. Immunocytochemical localization of calcium/calmodulin-dependent protein kinase II in rat brain. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5604–5608. doi: 10.1073/pnas.81.17.5604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Picciotto M. R., Czernik A. J., Nairn A. C. Calcium/calmodulin-dependent protein kinase I. cDNA cloning and identification of autophosphorylation site. J Biol Chem. 1993 Dec 15;268(35):26512–26521. [PubMed] [Google Scholar]
  37. Planas-Silva M. D., Means A. R. Expression of a constitutive form of calcium/calmodulin dependent protein kinase II leads to arrest of the cell cycle in G2. EMBO J. 1992 Feb;11(2):507–517. doi: 10.1002/j.1460-2075.1992.tb05081.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sahyoun N., McDonald O. B., Farrell F., Lapetina E. G. Phosphorylation of a Ras-related GTP-binding protein, Rap-1b, by a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2643–2647. doi: 10.1073/pnas.88.7.2643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schilling K., Luk D., Morgan J. I., Curran T. Regulation of a fos-lacZ fusion gene: a paradigm for quantitative analysis of stimulus-transcription coupling. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5665–5669. doi: 10.1073/pnas.88.13.5665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schulman H. The multifunctional Ca2+/calmodulin-dependent protein kinases. Curr Opin Cell Biol. 1993 Apr;5(2):247–253. doi: 10.1016/0955-0674(93)90111-3. [DOI] [PubMed] [Google Scholar]
  41. Sculptoreanu A., Scheuer T., Catterall W. A. Voltage-dependent potentiation of L-type Ca2+ channels due to phosphorylation by cAMP-dependent protein kinase. Nature. 1993 Jul 15;364(6434):240–243. doi: 10.1038/364240a0. [DOI] [PubMed] [Google Scholar]
  42. Sheng M., McFadden G., Greenberg M. E. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron. 1990 Apr;4(4):571–582. doi: 10.1016/0896-6273(90)90115-v. [DOI] [PubMed] [Google Scholar]
  43. Sheng M., Thompson M. A., Greenberg M. E. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991 Jun 7;252(5011):1427–1430. doi: 10.1126/science.1646483. [DOI] [PubMed] [Google Scholar]
  44. Silva A. J., Paylor R., Wehner J. M., Tonegawa S. Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science. 1992 Jul 10;257(5067):206–211. doi: 10.1126/science.1321493. [DOI] [PubMed] [Google Scholar]
  45. Silva A. J., Stevens C. F., Tonegawa S., Wang Y. Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science. 1992 Jul 10;257(5067):201–206. doi: 10.1126/science.1378648. [DOI] [PubMed] [Google Scholar]
  46. Suidan H. S., Murrell R. D., Tolkovsky A. M. Carbachol and bradykinin elevate cyclic AMP and rapidly deplete ATP in cultured rat sympathetic neurons. Cell Regul. 1991 Jan;2(1):13–25. doi: 10.1091/mbc.2.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Waeber G., Habener J. F. Nuclear translocation and DNA recognition signals colocalized within the bZIP domain of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB. Mol Endocrinol. 1991 Oct;5(10):1431–1438. doi: 10.1210/mend-5-10-1431. [DOI] [PubMed] [Google Scholar]
  49. Walton K. M., Rehfuss R. P., Chrivia J. C., Lochner J. E., Goodman R. H. A dominant repressor of cyclic adenosine 3',5'-monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the cAMP-mediated induction of the somatostatin promoter in vivo. Mol Endocrinol. 1992 Apr;6(4):647–655. doi: 10.1210/mend.6.4.1350057. [DOI] [PubMed] [Google Scholar]
  50. Wegner M., Cao Z., Rosenfeld M. G. Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta. Science. 1992 Apr 17;256(5055):370–373. doi: 10.1126/science.256.5055.370. [DOI] [PubMed] [Google Scholar]
  51. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]