ArticleMolecular cell2012
The Akt-SRPK-SR axis constitutes a major pathway in transducing EGF signaling to regulate alternative splicing in the nucleus.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 175 papers, 1 of them a synthesis that pooled it.
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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.
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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
175 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- Alternative Splicing of TPM1 Mediated by SRPK3 Drives Cardiac Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.Circulation · 2026Article
- An ultraconserved pseudo 5' splice site fine-tunes development by regulating alternative splicing within TOR-related pathways.Nature communications · 2026Article
- Phosphorylation-dependent regulation of serine/arginine-rich proteins and U2AF1 interactions in early spliceosome assembly.The Journal of biological chemistry · 2026Article
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Targeting SRPK3 Attenuates Cardiac Hypertrophy and Heart Failure by Improving Mitochondrial Bioenergetics through mRNA Splicing and Decay.Research (Washington, D.C.) · 2026Article
- Article
- API5 Phosphorylation Promotes Antiviral Immunity by Inhibiting Degradation of Cytosolic RNA Sensor RLRs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Viral Modulation of Host Splicing.Annual review of virology · 2025Review
- RNA-binding proteins and autophagy in lung cancer: mechanistic insights and therapeutic perspectives.Discover oncology · 2025Review
- The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer.Cell death & disease · 2025Review
- Real-World Evidence of Bevacizumab and Panitumumab Drug Resistance and Drug Ineffectiveness from EudraVigilance Database.Cancers · 2025Article
- Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modification.Nature neuroscience · 2025Article
- Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer.Cancers · 2025Review
- Potential antitumoral effects of SRPK1 inhibition through modulation of VEGF splicing in pituitary somatotroph tumoral cells.Frontiers in endocrinology · 2025Article
- PDGFRα signaling regulates Srsf3 transcript binding to affect PI3K signaling and endosomal trafficking.eLife · 2024Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Regulatory interplay between SR proteins governsRNA (New York, N.Y.) · 2024Article
- PDGFRα signaling regulates Srsf3 transcript binding to affect PI3K signaling and endosomal trafficking.bioRxiv : the preprint server for biology · 2024Article
- Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.Nature genetics · 2024Article
115 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Pre-mRNA splicing is regulated by developmental and environmental cues, but little is known about how specific signals are transduced in mammalian cells to regulate this critical gene expression step. Here, we report massive reprogramming of alternative splicing in response to EGF signaling. By blocking individual branches in EGF signaling, we found that Akt activation plays a major role, while other branches, such as the JAK/STAT and ERK pathways, make minor contributions to EGF-induced splicing. Activated Akt next branches to SR protein-specific kinases, rather than mTOR, by inducing SRPK autophosphorylation that switches the splicing kinases from Hsp70- to Hsp90-containing complexes. This leads to enhanced SRPK nuclear translocation and SR protein phosphorylation. These findings reveal a major signal transduction pathway for regulated splicing and place SRPKs in a central position in the pathway, consistent with their reputed roles in a large number of human cancers.
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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.