Abstract
Calcium influx in response to extracellular signals can modulate gene transcription. A constitutive, calcium/calmodulin-independent mutant of type II calcium/calmodulin-dependent protein kinase was capable of increasing the transcription rate of specific genes independently of protein kinase C activation. This increase was mediated by transferable cis-active elements capable of binding the transcription factor CAAT/enhancer binding protein. Therefore, the activation of type II calcium/calmodulin-dependent protein kinase in response to stimuli that increase intracellular calcium is proposed to represent a distinct second messenger pathway in calcium-mediated regulation of gene transcription.
Full text
PDF![3710](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce28/51522/8f39b8613733/pnas01059-0210.png)
![3711](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce28/51522/040fa5eec793/pnas01059-0211.png)
![3712](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce28/51522/e9c2495e7816/pnas01059-0212.png)
![3713](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce28/51522/a719a7449f2b/pnas01059-0213.png)
![3714](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce28/51522/f4a8bc7eae9e/pnas01059-0214.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cullen B. R., Raymond K., Ju G. Functional analysis of the transcription control region located within the avian retroviral long terminal repeat. Mol Cell Biol. 1985 Mar;5(3):438–447. doi: 10.1128/mcb.5.3.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Day R. N., Maurer R. A. Pituitary calcium channel modulation and regulation of prolactin gene expression. Mol Endocrinol. 1990 May;4(5):736–742. doi: 10.1210/mend-4-5-736. [DOI] [PubMed] [Google Scholar]
- Enyeart J. J., Biagi B., Day R. N. Opposing actions of Bay K 8644 enantiomers on calcium current, prolactin secretion, and synthesis in pituitary cells. Mol Endocrinol. 1990 May;4(5):727–735. doi: 10.1210/mend-4-5-727. [DOI] [PubMed] [Google Scholar]
- Giguère V., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Functional domains of the human glucocorticoid receptor. Cell. 1986 Aug 29;46(5):645–652. doi: 10.1016/0092-8674(86)90339-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greengard P. Phosphorylated proteins as physiological effectors. Science. 1978 Jan 13;199(4325):146–152. doi: 10.1126/science.22932. [DOI] [PubMed] [Google Scholar]
- Hanson P. I., Kapiloff M. S., Lou L. L., Rosenfeld M. G., Schulman H. Expression of a multifunctional Ca2+/calmodulin-dependent protein kinase and mutational analysis of its autoregulation. Neuron. 1989 Jul;3(1):59–70. doi: 10.1016/0896-6273(89)90115-3. [DOI] [PubMed] [Google Scholar]
- Hatada Y., Munemura M., Fukunaga K., Yamamoto H., Maeyama M., Miyamoto E. Calmodulin and Ca2+- and calmodulin-dependent protein kinase in rat anterior pituitary gland. J Neurochem. 1983 Apr;40(4):1082–1089. doi: 10.1111/j.1471-4159.1983.tb08096.x. [DOI] [PubMed] [Google Scholar]
- Hinkle P. M., Jackson A. E., Thompson T. M., Zavacki A. M., Coppola D. A., Bancroft C. Calcium channel agonists and antagonists: effects of chronic treatment on pituitary prolactin synthesis and intracellular calcium. Mol Endocrinol. 1988 Nov;2(11):1132–1138. doi: 10.1210/mend-2-11-1132. [DOI] [PubMed] [Google Scholar]
- Ingraham H. A., Chen R. P., Mangalam H. J., Elsholtz H. P., Flynn S. E., Lin C. R., Simmons D. M., Swanson L., Rosenfeld M. G. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell. 1988 Nov 4;55(3):519–529. doi: 10.1016/0092-8674(88)90038-4. [DOI] [PubMed] [Google Scholar]
- Klein-Hitpass L., Schorpp M., Wagner U., Ryffel G. U. An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 1986 Sep 26;46(7):1053–1061. doi: 10.1016/0092-8674(86)90705-1. [DOI] [PubMed] [Google Scholar]
- Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
- Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
- Lin C. R., Kapiloff M. S., Durgerian S., Tatemoto K., Russo A. F., Hanson P., Schulman H., Rosenfeld M. G. Molecular cloning of a brain-specific calcium/calmodulin-dependent protein kinase. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5962–5966. doi: 10.1073/pnas.84.16.5962. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Llinás R., McGuinness T. L., Leonard C. S., Sugimori M., Greengard P. Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sci U S A. 1985 May;82(9):3035–3039. doi: 10.1073/pnas.82.9.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loeffler J. P., Kley N., Louis J. C., Demeneix B. A. Ca2+ regulates hormone secretion and proopiomelanocortin gene expression in melanotrope cells via the calmodulin and the protein kinase C pathways. J Neurochem. 1989 Apr;52(4):1279–1283. doi: 10.1111/j.1471-4159.1989.tb01876.x. [DOI] [PubMed] [Google Scholar]
- Malinow R., Schulman H., Tsien R. W. Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. Science. 1989 Aug 25;245(4920):862–866. doi: 10.1126/science.2549638. [DOI] [PubMed] [Google Scholar]
- Mangalam H. J., Albert V. R., Ingraham H. A., Kapiloff M., Wilson L., Nelson C., Elsholtz H., Rosenfeld M. G. A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally. Genes Dev. 1989 Jul;3(7):946–958. doi: 10.1101/gad.3.7.946. [DOI] [PubMed] [Google Scholar]
- Maurer R. A. Both isoforms of the cAMP-dependent protein kinase catalytic subunit can activate transcription of the prolactin gene. J Biol Chem. 1989 Apr 25;264(12):6870–6873. [PubMed] [Google Scholar]
- 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]
- Morgan J. I., Curran T. Role of ion flux in the control of c-fos expression. Nature. 1986 Aug 7;322(6079):552–555. doi: 10.1038/322552a0. [DOI] [PubMed] [Google Scholar]
- Nelson C., Albert V. R., Elsholtz H. P., Lu L. I., Rosenfeld M. G. Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science. 1988 Mar 18;239(4846):1400–1405. doi: 10.1126/science.2831625. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
- Parker P. J., Kour G., Marais R. M., Mitchell F., Pears C., Schaap D., Stabel S., Webster C. Protein kinase C--a family affair. Mol Cell Endocrinol. 1989 Aug;65(1-2):1–11. doi: 10.1016/0303-7207(89)90159-7. [DOI] [PubMed] [Google Scholar]
- Patton B. L., Miller S. G., Kennedy M. B. Activation of type II calcium/calmodulin-dependent protein kinase by Ca2+/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain. J Biol Chem. 1990 Jul 5;265(19):11204–11212. [PubMed] [Google Scholar]
- Ryden T. A., Beemon K. Avian retroviral long terminal repeats bind CCAAT/enhancer-binding protein. Mol Cell Biol. 1989 Mar;9(3):1155–1164. doi: 10.1128/mcb.9.3.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schulman H., Kuret J., Jefferson A. B., Nose P. S., Spitzer K. H. Ca2+/calmodulin-dependent microtubule-associated protein 2 kinase: broad substrate specificity and multifunctional potential in diverse tissues. Biochemistry. 1985 Sep 24;24(20):5320–5327. doi: 10.1021/bi00341a008. [DOI] [PubMed] [Google Scholar]
- Schulman H. The multifunctional Ca2+/calmodulin-dependent protein kinase. Adv Second Messenger Phosphoprotein Res. 1988;22:39–112. [PubMed] [Google Scholar]
- Sealey L., Chalkley R. At least two nuclear proteins bind specifically to the Rous sarcoma virus long terminal repeat enhancer. Mol Cell Biol. 1987 Feb;7(2):787–798. doi: 10.1128/mcb.7.2.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
- Tabor S., Richardson C. C. A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1074–1078. doi: 10.1073/pnas.82.4.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waldmann R., Hanson P. I., Schulman H. Multifunctional Ca2+/calmodulin-dependent protein kinase made Ca2+ independent for functional studies. Biochemistry. 1990 Feb 20;29(7):1679–1684. doi: 10.1021/bi00459a002. [DOI] [PubMed] [Google Scholar]
- Waterman M. L., Adler S., Nelson C., Greene G. L., Evans R. M., Rosenfeld M. G. A single domain of the estrogen receptor confers deoxyribonucleic acid binding and transcriptional activation of the rat prolactin gene. Mol Endocrinol. 1988 Jan;2(1):14–21. doi: 10.1210/mend-2-1-14. [DOI] [PubMed] [Google Scholar]
- Waxham M. N., Aronowski J., Kelly P. T. Functional analysis of Ca2+/calmodulin-dependent protein kinase II expressed in bacteria. J Biol Chem. 1989 May 5;264(13):7477–7482. [PubMed] [Google Scholar]
- White B. A. Evidence for a role of calmodulin in the regulation of prolactin gene expression. J Biol Chem. 1985 Jan 25;260(2):1213–1217. [PubMed] [Google Scholar]
- 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]