Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells
Open accessAbstract
Dyrk is a dual specific protein kinase thought to be involved in normal embryo neurogenesis and brain development. Defects/imperfections in this kinase have been suggested to play an important role in the mental retardation of patients with Down's syndrome. The transcriptional factor cAMP response element-binding protein (CREB) has been implicated in the formation of many types of synaptic plasticity, such as learning and memory. In the present study we show that Dyrk1 activity is markedly induced during the differentiation of immortalized hippocampal progenitor (H19-7) cells. The addition of a neurogenic factor, basic fibroblast growth factor, to the H19-7 cells results in an increased specific binding of Dyrk1 to active CREB. In addition, Dyrk1 directly phosphorylates CREB, leading to the stimulation of subsequent CRE-mediated gene transcription during the neuronal differentiation in H19-7 cells. Blockade of Dyrk1 activation significantly inhibits the neurite outgrowth as well as CREB phosphorylation induced by basic fibroblast growth factor. These findings suggest that Dyrk1 activation and subsequent CREB phosphorylation is important in the neuronal differentiation of central nervous system hippocampal cells.
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Expression of MNB/DYRK1A or Dyrk1a induces neuronal differentiation in neural cell lines.
“Expression of MNB/DYRK1A or Dyrk1a induces neuronal differentiation in neural cell lines (Kelly and Rahmani, 2005; Yang et al., 2001)”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Yang et al., 2001
The Results (page not supplied) explicitly report that transient expression of wild-type Dyrk1 had no apparent effect on neuronal differentiation in H19-7 cells. The paper instead finds that kinase-deficient Dyrk1 reduces differentiation induced by bFGF, supporting a role for Dyrk1 activity but not the claim that its expression induces differentiation. (LLM, conf=0.88)
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References 35 · Cited by 172
Research works printed but not linked: 4
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- Authors
- Yang, E. J., Ahn, Y. S., & Chung, K. C.
- Affiliations
- Yonsei University (KR)
- Corresponding author
- Chung, Kwang Chul
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 276
- Issue
- 43
- Pages
- 39819-39824
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2007124162
- Cited by
- 172
- References
- 35
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 8 · 2021: 8 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 9 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 8
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- CREB phosphorylation, neuronal differentiation, hippocampal progenitor cells, basic fibroblast growth factor, neurite outgrowth, Down syndrome, synaptic plasticity
- MeSH terms
- Dyrk Kinases, Animals, Cell Differentiation, Down Syndrome, Hippocampus, Humans, Neurons, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Stem Cells, Transcription, Genetic, Fibroblast Growth Factor 2, Protein Serine-Threonine Kinases, Cyclic AMP Response Element-Binding Protein, Gene Expression Regulation, Developmental, Two-Hybrid System Techniques, Rats
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