ArticleThe Journal of biological chemistry2009
The phosphatidylinositol 3-kinase/Akt pathway regulates transforming growth factor-{beta} signaling by destabilizing ski and inducing Smad7.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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
11 citing papers in PubMed, 28 citations in OpenAlex.
- Noggin promotes osteogenesis in human adipose-derived mesenchymal stem cells via FGFR2/Src/Akt and ERK signaling pathway.Scientific reports · 2024Article
- Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway.International journal of oncology · 2020Article
- AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4.BMC cell biology · 2015Article
- Increased mast cell numbers in a calcaneal tendon overuse model.Scandinavian journal of medicine & science in sports · 2013Article
- Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer.Virology · 2013Article
- SnoN oncoprotein enhances estrogen receptor-α transcriptional activity.Cellular signalling · 2012Article
- Cross-species functional genomic analysis identifies resistance genes of the histone deacetylase inhibitor valproic acid.PloS one · 2012Article
- Identification of Ski as a target for Aurora A kinase.Biochemical and biophysical research communications · 2011Article
- Crosstalk of TGF-β and estrogen receptor signaling in breast cancer.Journal of mammary gland biology and neoplasia · 2011Review
- TGF-β inhibits muscle differentiation by blocking autocrine signaling pathways initiated by IGF-II.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease.Signal transduction and targeted therapyArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ski is an oncoprotein that negatively regulates transforming growth factor (TGF)-beta signaling. It acts as a transcriptional co-repressor by binding to TGF-beta signaling molecules, Smads. Efficient TGF-beta signaling is facilitated by rapid proteasome-mediated degradation of Ski by TGF-beta. Here we report that Ski is phosphorylated by Akt/PKB kinase. Akt phosphorylates Ski on a highly conserved Akt motif at threonine 458 both in vitro and in vivo. The phosphorylation of Ski at threonine 458 is induced by Akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of Ski causes its destabilization and reduces Ski-mediated inhibition of expression of another negative regulator of TGF-beta, Smad7. Induction of Smad7 levels leads to inactivation of TGF-beta receptors and TGF-beta signaling cascade, as indicated by reduced induction of TGF-beta target p15. Therefore, Akt modulates TGF-beta signaling by temporarily adjusting the levels of two TGF-beta pathway negative regulators, Ski and Smad7. These novel findings demonstrate that Akt pathway activation directly impacts TGF-beta pathway.
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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.