ArticleArteriosclerosis, thrombosis, and vascular biology2009
PKA-dependent phosphorylation of serum response factor inhibits smooth muscle-specific gene expression.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases.Vascular pharmacology · 2024Review
- Lysine methylation signaling in skeletal muscle biology: from myogenesis to clinical insights.The Biochemical journal · 2023Review
- 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-MRTF signaling suppresses brown adipocyte development by modulating TGF-β/BMP pathway.Molecular and cellular endocrinology · 2020Article
- Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas.Nature medicine · 2018Article
- Redox regulation of the actin cytoskeleton and its role in the vascular system.Free radical biology & medicine · 2017Review
- Protein kinase A-mediated phosphorylation of the Broad-Complex transcription factor in silkworm suppresses its transcriptional activity.The Journal of biological chemistry · 2017Article
- Olfactomedin 2 Regulates Smooth Muscle Phenotypic Modulation and Vascular Remodeling Through Mediating Runt-Related Transcription Factor 2 Binding to Serum Response Factor.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Origin and differentiation of vascular smooth muscle cells.The Journal of physiology · 2015Review
- The STARS signaling pathway: a key regulator of skeletal muscle function.Pflugers Archiv : European journal of physiology · 2014Review
- cAMP regulation of airway smooth muscle function.Pulmonary pharmacology & therapeutics · 2013Review
- Serum response factor regulates expression of phosphatase and tensin homolog through a microRNA network in vascular smooth muscle cells.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
- Signaling mechanisms that regulate smooth muscle cell differentiation.Arteriosclerosis, thrombosis, and vascular biology · 2011Review
- NADPH oxidase 4 mediates TGF-β-induced smooth muscle α-actin via p38MAPK and serum response factor.Free radical biology & medicine · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveOur goal was to identify phosphorylation sites that regulate serum response factor (SRF) activity to gain a better understanding of the signaling mechanisms that regulate SRF's involvement in smooth muscle cell (SMC)-specific and early response gene expression. METHODS AND
resultsBy screening phosphorylation-deficient and mimetic mutations in SRF(-/-) embryonic stem cells, we identified T159 as a phosphorylation site that significantly inhibits SMC-specific gene expression in an embryonic stem cell model of SMC differentiation. This residue conforms to a highly conserved consensus cAMP-dependent protein kinase (PKA) site, and in vitro and in vivo labeling studies demonstrated that it was phosphorylated by PKA. Results from gel shift and chromatin immunoprecipitation assays demonstrated that T159 phosphorylation inhibited SRF binding to SMC-specific CArG elements. Interestingly, the myocardin factors could at least partially rescue the effects of the T159D mutation under some conditions, but this response was promoter specific. Finally, PKA signaling had much less of an effect on c-fos promoter activity and SRF binding to the c-fos CArG.
conclusionsOur results indicate that phosphorylation of SRF by PKA inhibits SMC-specific transcription suggesting a novel signaling mechanism for the control of SMC phenotype.
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Registered trials
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.