ArticleScience signaling2015
Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Review
- Single-cell transcriptomics identifies adipose tissue CD271Cell reports. Medicine · 2023Article
- Review
- Towards Understanding the Gene-Specific Roles of GATA Factors in Heart Development: Does GATA4 Lead the Way?International journal of molecular sciences · 2022Review
- Chemical-induced gene expression ranking and its application to pancreatic cancer drug repurposing.Patterns (New York, N.Y.) · 2022Article
- Transcription factor GATA6 promotes migration of human coronary artery smooth muscle cellsFrontiers in physiology · 2022Article
- Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling.Frontiers in cell and developmental biology · 2021Article
- Targeting smooth muscle cell phenotypic switching in vascular disease.JVS-vascular science · 2021Review
- The GATA Transcription Factor Gaf1 Represses tRNAs, Inhibits Growth, and Extends Chronological Lifespan Downstream of Fission Yeast TORC1.Cell reports · 2020Article
- Targeting GATA4 for cardiac repair.IUBMB life · 2020Review
- Nuclear Focal Adhesion Kinase Controls Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia Through GATA4-Mediated Cyclin D1 Transcription.Circulation research · 2019Article
- LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis.Circulation · 2019Article
- Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming.iScience · 2018Article
- Tollip Negatively Regulates Vascular Smooth Muscle Cell-Mediated Neointima Formation by Suppressing Akt-Dependent Signaling.Journal of the American Heart Association · 2018Article
- Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Opposing Actions of AKT (Protein Kinase B) Isoforms in Vascular Smooth Muscle Injury and Therapeutic Response.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree.eLife · 2017Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Vascular smooth muscle cells (VSMCs) undergo transcriptionally regulated reversible differentiation in growing and injured blood vessels. This dedifferentiation also contributes to VSMC hyperplasia after vascular injury, including that caused by angioplasty and stenting. Stents provide mechanical support and can contain and release rapamycin, an inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1). Rapamycin suppresses VSMC hyperplasia and promotes VSMC differentiation. We report that rapamycin-induced differentiation of VSMCs required the transcription factor GATA-6. Inhibition of mTORC1 stabilized GATA-6 and promoted the nuclear accumulation of GATA-6, its binding to DNA, its transactivation of promoters encoding contractile proteins, and its inhibition of proliferation. These effects were mediated by phosphorylation of GATA-6 at Ser(290), potentially by Akt2, a kinase that is activated in VSMCs when mTORC1 is inhibited. Rapamycin induced phosphorylation of GATA-6 in wild-type mice, but not in Akt2(-/-) mice. Intimal hyperplasia after arterial injury was greater in Akt2(-/-) mice than in wild-type mice, and the exacerbated response in Akt2(-/-) mice was rescued to a greater extent by local overexpression of the wild-type or phosphomimetic (S290D) mutant GATA-6 than by that of the phosphorylation-deficient (S290A) mutant. Our data indicated that GATA-6 and Akt2 are involved in the mTORC1-mediated regulation of VSMC proliferation and differentiation. Identifying the downstream transcriptional targets of mTORC1 may provide cell type-specific drug targets to combat cardiovascular diseases associated with excessive proliferation of VSMCs.
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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.