Serum‐ and glucocorticoid‐inducible kinase 1 enhances zif268 expression through the mediation of SRF and CREB1 associated with spatial memory formation
Abstract
Serum- and glucocorticoid-inducible kinase 1 (SGK1) has been shown to play an important role in spatial memory formation, but the molecular mechanism underlying this effect of SGK1 was not known. zif268 is an immediate early gene that is induced by water maze learning. To investigate the role of SGK1 in the regulation of zif268 expression, the dominant negative mutant of SGK1, SGK1 S422A, was infused to the hippocampal CA1 area of rats, and was found to decrease significantly the mRNA level of zif268 in both naïve animals and trained animals. SGK1 was also found to phosphorylate serum response factor (SRF) at Ser73, Ser75, and Ser99, and phosphorylate CREB1 at Ser133. Inhibition of SGK1 phosphorylation sites on SRF and CREB1 with alanine substitution significantly diminished SGK1-enhanced zif268 expression in the promoter-luciferase assay. SGK1 also phosphorylates Elk-1 and SGK1 phosphorylation of Elk-1 decreased the transcriptional activity of Elk-1. But SGK1 phosphorylation of Elk-1 did not affect SGK1-enhanced zif268 expression. Moreover, the phosphorylation of SGK1 was increased in rat CA1 area after water maze learning, accompanied by increased phosphorylation of SRF at Ser99 and increased phosphorylation of CREB1 at Ser133. All these effects were antagonized by SGK1 S422A transfection. These results together suggest that SGK1 enhances zif268 expression through the mediation of SRF and CREB1, and these signaling pathways are associated with spatial memory formation in ra…
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SGK1 plays a role in enhancing memory formation and reducing Aβ production, highlighting its potential in treatment of Alzheimer's disease.
“An increasing number of studies indicate that SGK1 plays a role in enhancing memory formation and reducing the production of Aβ, highlighting its potential in the treatment of AD”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Tyan et al., 2008
SGK1 increases neuronal plasticity by modulating SRF and CREB1, allowing transition of stored information from short-term to long-term memories.
“Specifically, SGK1 increases neuronal plasticity by modulating the activity of transcription factors SRF and CREB1. This process allows transitioning stored information from short-term memories to long-term memories”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Tyan et al., 2008
SGK1 enhances learning and memory capabilities in the water maze by phosphorylating transcription factors SRF and CREB1.
“In the context of spatial memory in the water maze, SGK1 enhances learning and memory capabilities by phosphorylating transcription factors such as Serum Response Factor (SRF) and cAMP Response Element-Binding Protein 1 (CREB1)”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Tyan et al., 2008
Cites
(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms
Lang, F., Böhmer, C., Palmada, M., Seebohm, G., Strutz-Seebohm, N., & Vallon, V. (2006) · Physiological Reviews · doi:10.1152/physrev.00050.2005 · Cited by 689 · see citing works
Ets ternary complex transcription factors
Buchwalter, G., Gross, C., & Wasylyk, B. (2004) · Gene · doi:10.1016/j.gene.2003.09.028 · Cited by 336 · cited 1× · see citing works
“The Ets-binding site is bound by ternary complex factors, such as Elk-1 (Buchwalter et al. 2004).”
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Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain
Howard, P. G., Zou, P., Zhang, Y., Huang, F., Tesic, V., Wu, C. Y.-C., & Lee, R. H.-C. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114973 · Cited by 13 · see citing works
Behavioral effects of SGK1 knockout in VTA and dopamine neurons
Doyle, M. A., Stark, A. R., Fejes-Tóth, G., Náray-Fejes-Tóth, A., & Mazei-Robison, M. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-71681-9 · Cited by 9 · see citing works
Liu, M., Lian, B., Lan, Z., Sun, H., Zhao, Y., Sun, T., Meng, Z., Zhao, C., & Zhang, J. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03690-1 · Cited by 8 · see citing works
- Authors
- Tyan, S., Tsai, M., Lin, C., Ma, Y., & Lee, E. H. Y.
- Affiliations
- National Defense Medical Center (TW)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Corresponding author
- Lee, Eminy H. Y.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-12-13
- Volume
- 105
- Issue
- 3
- Pages
- 820-832
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1979087914
- Cited by
- 31
- References
- 3
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2014: 1 · 2013: 2
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- SGK1, serum- and glucocorticoid-inducible kinase 1, Zif268, immediate early gene expression, SRF, CREB1, Elk-1, spatial memory, hippocampal CA1, water maze learning, transcriptional regulation, dominant-negative mutant
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Animals, Binding Sites, Cell Line, Gene Expression Regulation, Hippocampus, Humans, Memory, Phosphorylation, RNA, Messenger, Serine, Space Perception, Down-Regulation, PC12 Cells, Protein Serine-Threonine Kinases, Cyclic AMP Response Element-Binding Protein, Immediate-Early Proteins, Maze Learning, Serum Response Factor, ets-Domain Protein Elk-1, Rats, Early Growth Response Protein 1
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