Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins
Abstract
Select members of the Wnt family of secreted glycoproteins have been implicated in inducing the myogenic determinant genes Pax3, MyoD and Myf5 during mammalian embryogenesis, but the mechanism of induction has not been defined. We describe an unexpected role for protein kinase A (PKA) signalling via CREB in this induction. Using a combination of in vitro explant assays, mutant analysis and gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl cyclase signalling via PKA and its target transcription factor CREB are required for Wnt-directed myogenic gene expression. Wnt proteins can also stimulate CREB-mediated transcription, providing evidence for a Wnt signalling pathway involving PKA and CREB. Our findings raise the possibility that PKA/CREB signalling may also contribute to other Wnt-regulated processes in embryonic patterning, stem cell renewal and cancer.
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During myogenesis, Wnt signaling via PKA and the transcription factor CREB modulates gene transcription of muscle specific genes including MyoD and Myf5.
“During myogenesis, Wnt signaling via PKA and the transcription factor CREB modulates gene transcription of muscle specific genes including MyoD and Myf5.111”
From Wnt signal transduction pathways (2008) · cites this paper as [111]
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- Authors
- Chen, A. E., Ginty, D. D., & Fan, C.-M.
- Affiliations
- Carnegie Institution for Science (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fan, Chen-Ming
- Venue
- Nature
- Published
- 2004-11-28
- Volume
- 433
- Issue
- 7023
- Pages
- 317-322
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2073269248
- Cited by
- 309
- References
- 27
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 12 · 2019: 13 · 2018: 7 · 2017: 15 · 2016: 6 · 2015: 14 · 2014: 12 · 2013: 15 · 2012: 17
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- Wnt signaling, protein kinase A, CREB, myogenesis, Pax3, MyoD, Myf5, adenylate cyclase, transcriptional regulation, embryonic patterning
- MeSH terms
- PAX3 Transcription Factor, Adenylyl Cyclases, Animals, Cell Line, DNA-Binding Proteins, Muscle Proteins, Muscles, Mutation, RNA, Messenger, Transcription Factors, Signal Transduction, Trans-Activators, Cyclic AMP Response Element-Binding Protein, MyoD Protein, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, Gene Expression Regulation, Developmental, Coculture Techniques, Somites, Muscle Development, Intercellular Signaling Peptides and Proteins, Embryo Culture Techniques, Wnt Proteins, Mice, Paired Box Transcription Factors, Myogenic Regulatory Factor 5
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