ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
SRF phosphorylation by glycogen synthase kinase-3 promotes axon growth in hippocampal neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Fibroblast Growth Factor 21 Promotes Vascular Smooth Muscle Cell Contractile Polarization via p38 Mitogen-Activated Protein Kinase-Promoted Serum Response Factor Phosphorylation.Research (Washington, D.C.) · 2025Article
- The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.Acta pharmaceutica Sinica. B · 2024Article
- SRF deletion results in earlier disease onset in a mouse model of amyotrophic lateral sclerosis.JCI insight · 2023Article
- GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target.Cells · 2022Review
- SRF in Neurochemistry: Overview of Recent Advances in Research on the Nervous System.Neurochemical research · 2022Review
- SRF depletion in early life contributes to social interaction deficits in the adulthood.Cellular and molecular life sciences : CMLS · 2022Article
- Single-molecule tracking (SMT) and localization of SRF and MRTF transcription factors during neuronal stimulation and differentiation.Open biology · 2022Article
- Vinculin-mediated axon growth requires interaction with actin but not talin in mouse neocortical neurons.Cellular and molecular life sciences : CMLS · 2021Article
- Serum response factor-cofactor interactions and their implications in disease.The FEBS journal · 2021Review
- A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells.Frontiers in cell and developmental biology · 2021Article
- SRF and SRFΔ5 Splicing Isoform Recruit Corepressor LSD1/KDM1A Modifying Structural Neuroplasticity and Environmental Stress Response.Molecular neurobiology · 2020Article
- Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- PTEN-GSK3β-MOB1 axis controls neurite outgrowth in vitro and in vivo.Cellular and molecular life sciences : CMLS · 2018Article
- A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.BMC bioinformatics · 2018Article
- Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.Nature communications · 2018Article
- SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation.eLife · 2018Article
- Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins.Journal of visualized experiments : JoVE · 2018Article
- SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model.Molecular brain · 2017Article
- Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects.Neural regeneration research · 2017Article
- Role of hippocampal activity-induced transcription in memory consolidation.Reviews in the neurosciences · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The growth of axons is an intricately regulated process involving intracellular signaling cascades and gene transcription. We had previously shown that the stimulus-dependent transcription factor, serum response factor (SRF), plays a critical role in regulating axon growth in the mammalian brain. However, the molecular mechanisms underlying SRF-dependent axon growth remains unknown. Here we report that SRF is phosphorylated and activated by GSK-3 to promote axon outgrowth in mouse hippocampal neurons. GSK-3 binds to and directly phosphorylates SRF on a highly conserved serine residue. This serine phosphorylation is necessary for SRF activity and for its interaction with MKL-family cofactors, MKL1 and MKL2, but not with TCF-family cofactor, ELK-1. Axonal growth deficits caused by GSK-3 inhibition could be rescued by expression of a constitutively active SRF. The SRF target gene and actin-binding protein, vinculin, is sufficient to overcome the axonal growth deficits of SRF-deficient and GSK-3-inhibited neurons. Furthermore, short hairpin RNA-mediated knockdown of vinculin also attenuated axonal growth. Thus, our findings reveal a novel phosphorylation and activation of SRF by GSK-3 that is critical for SRF-dependent axon growth in mammalian central neurons.
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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.