ArticleProceedings of the National Academy of Sciences of the United States of America2011
Calpain interacts with class IA phosphoinositide 3-kinases regulating their stability and signaling activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases.Neurochemical research · 2022Pooled it
- The Piezo1-Ca2+-PI3k/Akt signaling axis as a context-dependent mechanotransduction node during skin wound healing.iScience · 2026Review
- Fedratinib treatment correlates with suppressed STAT3/AKT/calpain-1 signaling and inhibits hepatocellular carcinoma progression.Translational gastroenterology and hepatology · 2026Article
- Double vulnerability of active-NRF2 lung squamous cell carcinoma to NRF2 and TRIM24.Molecular cancer · 2025Article
- Environmental pollutants and phosphoinositide signaling in autoimmunity.Journal of hazardous materials · 2024Review
- Prevention of noise-induced hearing loss by calpain inhibitor MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathway.Frontiers in cellular neuroscience · 2023Article
- Myeloid cell-specific deletion of Capns1 prevents macrophage polarization toward the M1 phenotype and reduces interstitial lung disease in the bleomycin model of systemic sclerosis.Arthritis research & therapy · 2022Article
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- Quantitative Phosphoproteomics Reveals System-Wide Phosphorylation Network Altered by Spry in Mouse Mammary Stromal Fibroblasts.International journal of molecular sciences · 2019Article
- Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?Current neuropharmacology · 2019Review
- Article
- Calpain Cleaves Most Components in the Multiple Aminoacyl-tRNA Synthetase Complex and Affects Their Functions.The Journal of biological chemistry · 2015Article
- Astragalus saponins modulates colon cancer development by regulating calpain-mediated glucose-regulated protein expression.BMC complementary and alternative medicine · 2014Article
- Candida albicans and Candida parapsilosis rapidly up-regulate galectin-3 secretion by human gingival epithelial cells.Mycopathologia · 2014Article
- The impact of biosampling procedures on molecular data interpretation.Molecular & cellular proteomics : MCP · 2013Review
- Calpain-2-mediated PTEN degradation contributes to BDNF-induced stimulation of dendritic protein synthesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Class IA phosphoinositide 3-kinases (PI3Ks) are signaling enzymes with key roles in the regulation of essential cellular functions and disease, including cancer. Accordingly, their activity is tightly controlled in cells to maintain homeostasis. The formation of multiprotein complexes is a ubiquitous mechanism to regulate enzyme activity but the contribution of protein-protein interactions to the regulation of PI3K signaling is not fully understood. We designed an affinity purification quantitative mass spectrometry strategy to identify proteins interacting dynamically with PI3K in response to pathway activation, with the view that such binding partners may have a functional role in pathway regulation. Our study reveals that calpain small subunit 1 interacts with PI3K and that the association between these proteins is lower in cells stimulated with serum compared to starved cells. Calpain and PI3K activity assays confirmed these results, thus demonstrating that active calpain heterodimers associate dynamically with PI3K. In addition, calpains were found to cleave PI3K proteins in vitro (resulting in a reduction of PI3K lipid kinase activity) and to regulate endogenous PI3K protein levels in vivo. Further investigations revealed that calpains have a role in the negative regulation of PI3K/Akt pathway activity (as measured by Akt and ribosomal S6 phosphorylation) and that their inhibition promotes cell survival during serum starvation. These results indicate that the interaction between calpain and PI3K is a novel mechanism for the regulation of class IA PI3K stability and activity.
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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.