ArticleMolecular and cellular biology2005
Phosphatidylinositol 3-kinase/Akt induced by erythropoietin renders the erythroid differentiation factor GATA-1 competent for TIMP-1 gene transactivation.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis.Nature communications · 2021Trial
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process.Nature communications · 2023Article
- miRNA Expression Associated with HbF in Saudi Sickle Cell Anemia.Medicina (Kaunas, Lithuania) · 2022Article
- Congenital deficiency reveals critical role of ISG15 in skin homeostasis.The Journal of clinical investigation · 2022Article
- FAM122A Inhibits Erythroid Differentiation through GATA1.Stem cell reports · 2020Article
- Single-cell analyses demonstrate that a heme-GATA1 feedback loop regulates red cell differentiation.Blood · 2019Article
- The GATA factor revolution in hematology.Blood · 2017Review
- Distinct gene expression program dynamics during erythropoiesis from human induced pluripotent stem cells compared with adult and cord blood progenitors.BMC genomics · 2016Article
- Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway.Age (Dordrecht, Netherlands) · 2016Article
- Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells.Nature communications · 2016Article
- Erythropoietin and IGF-1 signaling synchronize cell proliferation and maturation during erythropoiesis.Genes & development · 2015Article
- GATA1 induces epithelial-mesenchymal transition in breast cancer cells through PAK5 oncogenic signaling.Oncotarget · 2015Article
- Essential Role of GATA2 in the Negative Regulation of Type 2 Deiodinase Gene by Liganded Thyroid Hormone Receptor β2 in Thyrotroph.PloS one · 2015Article
- Netrin-4 as a biomarker promotes cell proliferation and invasion in gastric cancer.Oncotarget · 2015Article
- FOXO3-mTOR metabolic cooperation in the regulation of erythroid cell maturation and homeostasis.American journal of hematology · 2014Article
- Transcriptional mechanisms underlying hemoglobin synthesis.Cold Spring Harbor perspectives in medicine · 2013Review
- AKT2 confers protection against aortic aneurysms and dissections.Circulation research · 2013Article
- Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs.International journal of hematology-oncology and stem cell research · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The contribution of erythropoietin to the differentiation of the red blood cell lineage remains elusive, and the demonstration of a molecular link between erythropoietin and the transcription of genes associated with erythroid differentiation is lacking. In erythroid cells, expression of the tissue inhibitor of matrix metalloproteinase (TIMP-1) is strictly dependent on erythropoietin. We report here that erythropoietin regulates the transcription of the TIMP-1 gene upon binding to its receptor in erythroid cells by triggering the activation of phosphatidylinositol 3-kinase (PI3K)/Akt. We found that Akt directly phosphorylates the transcription factor GATA-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the TIMP-1 promoter. This chain of events can be recapitulated in nonerythroid cells by transfection of the implicated molecular partners, resulting in the expression of the normally silent endogenous TIMP-1 gene. Conversely, TIMP-1 secretion is profoundly decreased in erythroid cells from fetal livers of transgenic knock-in mice homozygous for a GATA(S310A) gene, which encodes a GATA-1 mutant that cannot be phosphorylated at Ser(310). Furthermore, retrovirus-mediated expression of GATA(S310A) into GATA-1(null)-derived embryonic stem cells decreases the rate of hemoglobinization by more than 50% compared to expressed wild-type GATA-1. These findings provide the first example of a chain of coupling mechanisms between the binding of erythropoietin to its receptor and GATA-1-dependent gene expression.
Indexed as
Identifiers
What OpenQuestion holds
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.