The Steroid Hormone 20-Hydroxyecdysone Enhances Gene Transcription through the cAMP Response Element-binding Protein (CREB) Signaling Pathway
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Animal steroid hormones regulate gene transcription through genomic pathways by binding to nuclear receptors. These steroid hormones also rapidly increase intracellular calcium and cyclic adenosine monophosphate (cAMP) levels and activate the protein kinase C (PKC) and protein kinase A (PKA) nongenomic pathways. However, the function and mechanism of the nongenomic pathways of the steroid hormones are unclear, and the relationship between the PKC and PKA pathways is also unclear. We propose that the steroid hormone 20-hydroxyecdysone (20E) activates the PKA pathway to enhance 20E-induced gene transcription in the lepidopteran insect Helicoverpa armigera The expression of the catalytic subunit 1 of PKA (PKAC1) increased during metamorphosis, and PKAC1 knockdown blocked pupation and repressed 20E-responsive gene expression. 20E regulated PKAC1 phosphorylation at threonine 200 and nuclear translocation through an ecdysone-responsive G-protein-coupled receptor 2. PKAC1 induced cAMP response element-binding protein (CREB) phosphorylation at serine 143, which bound to the cAMP response element on DNA to enhance 20E-responsive gene transcription. Through ecdysone-responsive G-protein-coupled receptor 2, 20E increased cAMP levels, which induced CREB PKA phosphorylation and 20E-responsive gene expression. This study demonstrates that the PKA/CREB pathway tightly and critically regulates 20E-induced gene transcription as well as its relationship with the 20E-induced PKC pathway.
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The 20E-induced PKA/CREB pathway enhances the 20E-induced PKC pathway for gene transcription.
“Thus, the 20E-induced PKA/CREB pathway enhances the 20E-induced PKC pathway for gene transcription [61].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [61]
20E stimulates a rapid increase in cAMP levels and activates the protein kinase A (PKA) pathway in H. armigera.
“In addition to triggering rapid increases in intracellular Ca2+ levels to activate the PKC pathway, 20E also stimulates a rapid increase in cAMP levels and activates the protein kinase A (PKA) pathway in H. armigera [61].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [61]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262 · see citing works
G PROTEINS: TRANSDUCERS OF RECEPTOR-GENERATED SIGNALS
Gilman, A. G. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.003151 · Cited by 6,405 · see citing works
Auphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., & Karin, M. (1995) · Science · doi:10.1126/science.270.5234.286 · Cited by 2,390 · see citing works
Function and regulation of CREB family transcription factors in the nervous system
Lonze, B. E., & Ginty, D. D. (2002) · Neuron · doi:10.1016/s0896-6273(02)00828-0 · Cited by 2,127 · see citing works
Nuclear Hormone Receptors and Gene Expression
Aranda, A., & Pascual, A. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.3.1269 · Cited by 1,562 · see citing works
Chijiwa, T., Mishima, A., Hagiwara, M., Sano, M., Hayashi, K., Inoue, T., NAITO, K., Toshioka, T., & Hidaka, H. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)34116-x · Cited by 1,486 · see citing works
Identification of a cyclic-AMP-responsive element within the rat somatostatin gene.
Montminy, M., Sevarino, K. A., Wagner, J. A., Mandel, G., & Goodman, R. H. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.18.6682 · Cited by 1,385 · see citing works
Carlezon, W. A., Duman, R. S., & Nestler, E. J. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.06.005 · Cited by 1,351 · see citing works
Nuclear Receptors, RXR, and the Big Bang
Evans, R. M., & Mangelsdorf, D. J. (2014) · Cell · doi:10.1016/j.cell.2014.03.012 · Cited by 1,200 · see citing works
Biological Actions of Androgens
MOORADIAN, A. D., MORLEY, J. E., & KORENMAN, S. G. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-1-1 · Cited by 1,080 · see citing works
Hall, J. M., & McDonnell, D. P. (1999) · Endocrinology · doi:10.1210/endo.140.12.7179 · Cited by 1,078 · see citing works
Koelle, M. R., Talbot, W. S., Segraves, W. A., Bender, M. T., Cherbas, P. T., & Hogness, D. S. (1991) · Cell · doi:10.1016/0092-8674(91)90572-g · Cited by 978 · see citing works
Filardo, E. J., Quinn, J. A., Frackelton, A. R., & Bland, K. I. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.1.0758 · Cited by 907 · see citing works
Radhakrishnan, I., Pérez-Alvarado, G. C., Parker, D., Dyson, H. J., Montminy, M. R., & Wright, P. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80463-8 · Cited by 728 · see citing works
Drosophila ultraspiracle modulates ecdysone receptor function via heterodimer formation
Yao, T., Segraves, W. A., Oro, A. E., McKeown, M., & Evans, R. M. (1992) · Cell · doi:10.1016/0092-8674(92)90266-f · Cited by 716 · see citing works
Estrogen Signaling Multiple Pathways to Impact Gene Transcription
Marino, M., Galluzzo, P., & Ascenzi, P. (2006) · Current Genomics · doi:10.2174/138920206779315737 · Cited by 618 · see citing works
Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model
Norman, A. W., Mizwicki, M. T., & Norman, D. P. G. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1283 · Cited by 569 · see citing works
Riddiford, L. M., Hiruma, K., Zhou, X., & Nelson, C. A. (2003) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2003.06.001 · Cited by 547 · see citing works
Control and biochemical nature of the ecdysteroidogenic pathway
Gilbert, L. I., Rybczynski, R., & Warren, J. T. (2002) · Annual Review of Entomology · doi:10.1146/annurev.ento.47.091201.145302 · Cited by 532 · see citing works
Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle
Thomas, H. E., Stunnenberg, H. G., & Stewart, A. F. (1993) · Nature · doi:10.1038/362471a0 · Cited by 520 · see citing works
Sumi, M., Kiuchi, K., Ishikawa, T., Ishii, A., Hagiwara, M., Nagatsu, T., & Hidaka, H. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)92031-e · Cited by 511 · see citing works
Hagiwara, M., Brindle, P. K., Harootunian, A. T., Armstrong, R., Rivier, J., Vale, W., Tsien, R. Y., & Montminy, M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4852-4859.1993 · Cited by 452 · see citing works
Regulation of camp-inducible genes by creb
Montminy, M., González, G., & Yamamoto, K. K. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90045-c · Cited by 419 · see citing works
Bartsch, D., Casadio, A., Karl, K. A., Serodio, P., & Kandel, E. R. (1998) · Cell · doi:10.1016/s0092-8674(00)81752-3 · Cited by 373 · see citing works
CREB: A mediator of long-term memory from mollusks to mammals
Frank, D. A., & Greenberg, M. E. (1994) · Cell · doi:10.1016/0092-8674(94)90394-8 · Cited by 369 · see citing works
The cAMP signalling pathway activates CREB through PKA, p38 and MSK1 in NIH 3T3 cells
Delghandi, M. P., Johannessen, M., & Moens, U. L. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.02.003 · Cited by 334 · see citing works
Srivastava, D. P., Yu, E. J., Kennedy, K., Chatwin, H., Reale, V., Hamon, M., Smith, T., & Evans, P. D. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1005-05.2005 · Cited by 272 · see citing works
Phosphorylation of Human Estrogen Receptor α by Protein Kinase A Regulates Dimerization
Chen, D., Pace, P. E., Coombes, R. C., & Ali, S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1002 · Cited by 258 · see citing works
Cheng, X., Ma, Y., Moore, M. J., Hemmings, B. A., & Taylor, S. S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.9849 · Cited by 248 · see citing works
A Novel EPAC-Specific Inhibitor Suppresses Pancreatic Cancer Cell Migration and Invasion
Almahariq, M. F., Tsalkova, T. N., Mei, F. C., Chen, H., Zhou, J., Sastry, S. K., Schwede, F., & Cheng, X. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.080689 · Cited by 207 · see citing works
Harootunian, A. T., Adams, S., Wen, W., et al. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.10.993 · Cited by 175 · see citing works
Horner, M. A., Chen, T., & Thummel, C. S. (1995) · Developmental Biology · doi:10.1006/dbio.1995.1097 · Cited by 171 · see citing works
Steroid signaling in plants and insects—common themes, different pathways
Thummel, C. S., & Chory, J. (2002) · Genes & Development · doi:10.1101/gad.1042102 · Cited by 161 · see citing works
Steinberg, R. A., Cauthron, R. D., Symcox, M. M., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.4.2332 · Cited by 144 · see citing works
Phosphorylation Modulates Catalytic Function and Regulation in the cAMP-Dependent Protein Kinase
Adams, J. A., McGlone, M. L., Gibson, R. M., & Taylor, S. S. (1995) · Biochemistry · doi:10.1021/bi00008a007 · Cited by 132 · see citing works
Geller, R. G., Margolius, H. S., Pisano, J. J., et al. (1972) · Circulation Research · doi:10.1161/01.res.31.6.857 · Cited by 132 · see citing works
Smallridge, R. C., Kiang, J. G., Gist, I. D., et al. (1992) · Endocrinology · doi:10.1210/endo.131.4.1396332 · Cited by 126 · see citing works
Lam, G., Hall, B. L., Bender, M., & Thummel, C. S. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9343 · Cited by 124 · see citing works
Ishimoto, H., Sakai, T., & Kitamoto, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810213106 · Cited by 122 · see citing works
Sandén, C., Broselid, S., Cornmark, L., Andersson, K. A., Daszkiewicz-Nilsson, J., Mårtensson, U. E. A., Olde, B., & Leeb-Lundberg, L. M. F. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.069500 · Cited by 121 · see citing works
Phosphorylation of the Catalytic Subunit of Protein Kinase A
Moore, M. J., Kanter, J. R., Jones, K., & Taylor, S. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204970200 · Cited by 116 · see citing works
Lan, Q., Hiruma, K., Hu, X., Jindra, M., & Riddiford, L. M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.7.4897 · Cited by 107 · see citing works
Butterworth, J. F. I., Brownlow, R. C., Leith, J. P., et al. (1993) · Anesthesiology · doi:10.1097/00000542-199307000-00014 · Cited by 106 · see citing works
Zhao, X., Wang, J., & Wang, Y.-C. (1998) · Insect Biochemistry and Molecular Biology · doi:10.1016/s0965-1748(98)00015-0 · Cited by 80 · see citing works
Self-citationEstablishment of a New Cell Line from Lepidopteran Epidermis and Hormonal Regulation on the Genes
Shao, H., Zheng, W., Liu, P., Wang, Q., Wang, J., & Zhao, X. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003127 · Cited by 79 · see citing works
Self-citationNahar, J., Haam, J., Chen, C., Jiang, Z., Glatzer, N. R., Muglia, L. J., Dohanich, G. P., Herman, J. P., & Tasker, J. G. (2015) · Endocrinology · doi:10.1210/en.2015-1273 · Cited by 77 · see citing works
Koga, T., Mizui, M., Yoshida, N., et al. (2014) · Autoimmunity · doi:10.3109/08916934.2014.915954 · Cited by 69 · see citing works
Jian, D., Jiang, D., Su, J., Chen, W., Hu, X., Kuang, Y., Xie, H., Li, J., & Chen, X. (2011) · Steroids · doi:10.1016/j.steroids.2011.06.008 · Cited by 68 · see citing works
CREB Signaling-Timing Is Everything
Impey, S., & Goodman, R. H. (2001) · Science s STKE · doi:10.1126/stke.2001.82.pe1 · Cited by 66 · see citing works
Cruz, J., Martı́n, D., & Bellés, X. (2006) · Mechanisms of Development · doi:10.1016/j.mod.2006.12.003 · Cited by 64 · see citing works
PKA phosphorylation of the small heat-shock protein Hsp20 enhances its cardioprotective effects
Edwards, H. V., Scott, J. D., & Baillie, G. S. (2012) · Biochemical Society Transactions · doi:10.1042/bst20110673 · Cited by 61 · see citing works
Liu, W., Cai, M.-J., Zheng, C.-C., Wang, J.-X., & Zhao, X.-F. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.547018 · Cited by 59 · see citing works
Self-citationNongenomic action of an insect steroid hormone in steroid-induced programmed cell death
Iga, M., Iwami, M., & Sakurai, S. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.08.005 · Cited by 59 · see citing works
Suramin Disrupts Receptor-G Protein Coupling by Blocking Association of G Protein α and βγ Subunits
Chung, W.-C., & Kermode, J. C. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.078311 · Cited by 59 · see citing works
Kraft, R., Escobar, M. M., Narro, M. L., Kurtis, J. L., Efrat, A., Barnard, K., & Restifo, L. L. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2106-06.2006 · Cited by 57 · see citing works
Presence of membrane ecdysone receptor in the anterior silk gland of the silkworm <i>Bombyx mori</i>
Elmogy, M., Iwami, M., & Sakurai, S. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04249.x · Cited by 57 · see citing works
cAMP: Novel concepts in compartmentalised signalling
Edwards, H. V., Frank, C., & Baillie, G. S. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.09.005 · Cited by 55 · see citing works
Liu, W., Zhang, F., Cai, M., Zhao, W.-L., Li, X.-R., Wang, J., & Zhao, X. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.06.037 · Cited by 51 · see citing works
Self-citationEdwards, H. V., Scott, J. D., & Baillie, G. S. (2012) · Biochemical Journal · doi:10.1042/bj20120570 · Cited by 49 · see citing works
Chelerythrine, a protein kinase C inhibitor, interacts with cyclic nucleotide phosphodiesterases
Eckly‐Michel, A., Bec, A. L., & Lugnier, C. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)00149-0 · Cited by 45 · see citing works
G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane
Cai, M.-J., Dong, D.-J., Wang, Y., Liu, P.-C., Liu, W., Wang, J.-X., & Zhao, X.-F. (2014) · Cell Communication and Signaling · doi:10.1186/1478-811x-12-9 · Cited by 44 · see citing works
Self-citationMané‐Padrós, D., Cruz, J., Cheng, A., & Raikhel, A. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045019 · Cited by 39 · see citing works
Liu, W., Cai, M.-J., Wang, J.-X., & Zhao, X.-F. (2014) · Endocrinology · doi:10.1210/en.2013-2020 · Cited by 38 · see citing works
Self-citationLan, Q., Wu, Z., & Riddiford, L. M. (1997) · Insect Molecular Biology · doi:10.1046/j.1365-2583.1997.00151.x · Cited by 38 · see citing works
G-protein-coupled receptor controls steroid hormone signaling in cell membrane
Wang, D., Zhao, W.-L., Cai, M.-J., Wang, J.-X., & Zhao, X.-F. (2015) · Scientific Reports · doi:10.1038/srep08675 · Cited by 35 · cited 17× · see citing works
“To analyze the possible signaling pathways to activate CRE by 20E-induced CREB, the vector pCRE-IE1-RFP-His that only contains the CRE from the upstream region of HHR3 was con- JUNE 10, 2016 • VOLUME 291 • NUMBER 24 JOURNAL OF BIOLOGICAL CHEMISTRY 12779 structed by deleting the EcRE in pHR3-P-IE1-RFP-His (Fig.”
BackgroundInfluentialSelf-citationJing, Y.-P., Liu, W., Wang, J.-X., & Zhao, X.-F. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.622696 · Cited by 30 · see citing works
Self-citationClouse, S. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00549-8 · Cited by 22 · see citing works
El-Mogy, M. M., Terashima, J., Iga, M., Iwami, M., & Sakurai, S. (2006) · ZOOLOGICAL SCIENCE · doi:10.2108/zsj.23.715 · Cited by 18 · see citing works
G-protein αq participates in the steroid hormone 20-hydroxyecdysone nongenomic signal transduction
Ren, J., Li, X.-R., Liu, P.-C., Cai, M.-J., Liu, W., Wang, J.-X., & Zhao, X.-F. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.08.006 · Cited by 15 · see citing works
Self-citationA Functional Relay from Progesterone to Vitamin D in the Immune System
Kim, C. H. (2015) · DNA and Cell Biology · doi:10.1089/dna.2015.2857 · Cited by 14 · see citing works
Toi, M., Saeki, T., Iwata, H., Inoue, K., Tokuda, Y., Sato, Y., Ito, Y., Aogi, K., Takatsuka, Y., & Arioka, H. (2012) · Breast Cancer · doi:10.1007/s12282-012-0344-3 · Cited by 14 · see citing works
Shao, H., Zheng, W., Liu, P., et al. (2008) · PLoS ONE · doi:10.1371/annotation/5957bf19-a800-485d-aa5b-dfcdd095ca13 · Cited by 14 · see citing works
CREB isoform represses yolk protein gene expression in the mosquito fat body
Dittmer, N. T., Sun, G., Wang, S.-F., et al. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.08.010 · Cited by 11 · see citing works
G-protein-coupled receptor controls steroid hormone signaling in cell membrane
Wang, D. (2016) · International Congress of Entomology (ICE) · doi:10.1603/ice.2016.107278 · Cited by 4 · see citing works
Self-citationZhang, L., & lt (2015) · PubMed · doi:10.3969/j.issn.1671-167x.2015.03.022 · Cited by 2 · see citing works
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Self-citationZhao, X.-F. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00620-y · Cited by 60 · see citing works
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- Authors
- Jing, Y.-P., Wang, D., Han, X.-L., Dong, D.-J., Wang, J.-X., & Zhao, X.-F.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Zhao, Xiao-Fan
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 291
- Issue
- 24
- Pages
- 12771-12785
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4933448
- OpenAlex
- W2340838087
- Cited by
- 30
- References
- 76
- Citations by year
- 2025: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 5
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- 20-hydroxyecdysone, ecdysone, CREB, protein kinase A, non-genomic steroid action, gene transcription, Helicoverpa armigera, metamorphosis, pupation, protein kinase C, CREB phosphorylation, cyclic AMP
- MeSH terms
- Animals, Cell Line, Ecdysterone, Larva, Metamorphosis, Biological, Moths, Phosphorylation, Protein Binding, Protein Kinase C, Transcription, Genetic, Blotting, Western, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Gene Expression Regulation, Developmental, Insect Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference
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