The Steroid Hormone 20-Hydroxyecdysone via Nongenomic Pathway Activates Ca2+/Calmodulin-dependent Protein Kinase II to Regulate Gene Expression
Open accessAbstract
The steroid hormone 20-hydroxyecdysone (20E) triggers calcium signaling pathway to regulate 20E response gene expression, but the mechanism underlying this process remains unclear. We propose that the 20E-induced phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) serves an important function in 20E response gene transcription in the lepidopteran insect Helicoverpa armigera. CaMKII showed increased expression and phosphorylation during metamorphosis. 20E elevated CaMKII phosphorylation. However, the G protein-coupled receptor (GPCR) and ryanodine receptor inhibitor suramin, the phospholipase C inhibitor U73122, and the inositol 1,4,5-triphosphate receptor inhibitor xestospongin C suppressed 20E-induced CaMKII phosphorylation. Two ecdysone-responsible GPCRs and Gαq protein were involved in 20E-induced CaMKII phosphorylation by RNA interference analysis. 20E regulated CaMKII threonine phosphorylation at amino acid 290, thereby inducing CaMKII nuclear translocation. CaMKII knockdown by dsCaMKII injection into the larvae prevented the occurrence of larval-pupal transition and suppressed 20E response gene expression. CaMKII phosphorylation and nuclear translocation maintained USP1 lysine acetylation at amino acid 303 by inducing histone deacetylase 3 phosphorylation and nuclear export. The lysine acetylation of USP1 was necessary for the interaction of USP1 with EcRB1 and their binding to the ecdysone response element. Results suggest that 20E (via GPCR activation and calcium signaling) activates CaMKII phosphorylation and nuclear translocation, which regulate USP1 lysine acetylation to form an EcRB1-USP1 complex for 20E response gene transcription.
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USP lysine acetylation at amino acid 303 is necessary for its interaction with EcR to form the transcription complex and for the binding of the EcR-USP complex to EcRE.
“This modification is necessary for its interaction with EcR to form the transcription complex and for the binding of the EcR-USP complex to EcRE [56].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [56]
CaMKII expression and phosphorylation increase during metamorphosis in H. armigera.
“CaMKII expression and phosphorylation increase during metamorphosis in H. armigera [56].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [56]
The genomic action/pathway of 20E is regulated by the nongenomic action/pathway because the 20E-induced rapid calcium increase in cells activates protein kinases, thereby promoting EcR-USP transcription complex formation, which initiates gene transcription in the 20E pathway.
“From the studies in H. armigera, the genomic action/pathway of 20E is regulated by the nongenomic action/pathway, because the 20E-induced rapid calcium increase in cells activates protein kinases [52, 56], therefore promotes EcR-USP transcription complex formation, which initiates gene transcription in 20E pathway finally [64].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [56]
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- Authors
- Jing, Y.-P., Liu, W., Wang, J.-X., & Zhao, X.-F.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Zhao, Xiao-Fan
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 290
- Issue
- 13
- Pages
- 8469-8481
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4375498
- OpenAlex
- W2085211690
- Cited by
- 30
- References
- 52
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 3 · 2017: 2 · 2016: 3
- FWCI
- 0.77
- 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)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- 20-hydroxyecdysone, CaMKII, non-genomic steroid action, calcium signaling, G protein-coupled receptors, Gαq, ryanodine receptor, phospholipase C, IP3 receptor, USP1, lysine acetylation, HDAC3, ecdysone response element, gene transcription, metamorphosis, larval-pupal transition, Helicoverpa armigera, nuclear translocation
- MeSH terms
- Histone Deacetylase 3, Acetylation, Amino Acid Sequence, Animals, Cell Line, Cell Nucleus, Ecdysterone, Enzyme Activation, Histone Deacetylases, Metamorphosis, Biological, Molecular Sequence Data, Moths, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Gene Expression Regulation, Developmental, Insect Proteins, Response Elements, Active Transport, Cell Nucleus, Epigenesis, Genetic, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Ubiquitin-Specific Proteases
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