ArticleMolecular and cellular biology2008
Protein kinase A represses skeletal myogenesis by targeting myocyte enhancer factor 2D.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
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- The Novel MuRF2 Target SNX5 Regulates PKA Activity Through Stabilization of RI-α and Controls Myogenic Differentiation.Journal of cachexia, sarcopenia and muscle · 2025Article
- Combinatorial metabolomic and transcriptomic analysis of muscle growth in hybrid striped bass (female white bass Morone chrysops x male striped bass M. saxatilis).BMC genomics · 2024Article
- An upstream enhancer and MEF2 transcription factors fine-tune the regulation of the Bdnf gene in cortical and hippocampal neurons.The Journal of biological chemistry · 2024Article
- The Molecular and Biological Function of MEF2D in Leukemia.Advances in experimental medicine and biology · 2024Review
- Dopamine receptor D4 (DRD4) negatively regulates UCP1- and ATP-dependent thermogenesis in 3T3-L1 adipocytes and C2C12 muscle cells.Pflugers Archiv : European journal of physiology · 2023Article
- The MEF2A transcription factor interactome in cardiomyocytes.Cell death & disease · 2023Article
- The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration.International journal of molecular sciences · 2023Review
- Differential Response of Transcription Factors to Activated Kinases in Steroidogenic and Non-Steroidogenic Cells.International journal of molecular sciences · 2022Article
- Quantitative Proteome and Transcriptome Dynamics Analysis Reveals Iron Deficiency Response Networks and Signature in Neuronal Cells.Molecules (Basel, Switzerland) · 2022Article
- A Review of free fatty acid-induced cell signaling, angiopoietin-like protein 4, and skeletal muscle differentiation.Frontiers in physiology · 2022Review
- Comparison of Selection Signatures between Korean Native and Commercial Chickens Using 600K SNP Array Data.Genes · 2021Article
- Adaptive versus maladaptive cardiac remodelling in response to sustained β-adrenergic stimulation in a new 'ISO on/off model'.PloS one · 2021Article
- Article
- mTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4.Nature communications · 2019Article
- MEF-2 isoforms' (A-D) roles in development and tumorigenesis.Oncotarget · 2019Review
- βAnimal cells and systems · 2019Article
- Diversification of the muscle proteome through alternative splicing.Skeletal muscle · 2018Review
- Novel role and regulation of HDAC4 in cocaine-related behaviors.Addiction biology · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of protein kinase A (PKA) by elevation of the intracellular cyclic AMP (cAMP) level inhibits skeletal myogenesis. Previously, an indirect modulation of the myogenic regulatory factors (MRFs) was implicated as the mechanism. Because myocyte enhancer factor 2 (MEF2) proteins are key regulators of myogenesis and obligatory partners for the MRFs, here we assessed whether these proteins could be involved in PKA-mediated myogenic repression. Initially, in silico analysis revealed several consensus PKA phosphoacceptor sites on MEF2, and subsequent analysis by in vitro kinase assays indicated that PKA directly and efficiently phosphorylates MEF2D. Using mass spectrometric determination of phosphorylated residues, we document that MEF2D serine 121 and serine 190 are targeted by PKA. Transcriptional reporter gene assays to assess MEF2D function revealed that PKA potently represses the transactivation properties of MEF2D. Furthermore, engineered mutation of MEF2D PKA phosphoacceptor sites (serines 121 and 190 to alanine) rendered a PKA-resistant MEF2D protein, which efficiently rescues myogenesis from PKA-mediated repression. Concomitantly, increased intracellular cAMP-mediated PKA activation also resulted in an enhanced nuclear accumulation of histone deacetylase 4 (HDAC4) and a subsequent increase in the MEF2D-HDAC4 repressor complex. Collectively, these data identify MEF2D as a primary target of PKA signaling in myoblasts that leads to inhibition of the skeletal muscle differentiation program.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.