ArticleMolecular and cellular biology2004
Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 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
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases.Neurochemical research · 2022Pooled it
- MAP3K1: A Multifunctional Kinase at the Crossroads of Cancer Progression and Tumor Suppression.Cells · 2026Review
- Review
- Review
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Noncanonical altPIDD1 protein: unveiling the true major translational output of theLife science alliance · 2025Article
- Prime editing in mice with an engineered pegRNA.Vascular pharmacology · 2024Article
- The neuronal transcription factor MEIS2 is a calpain-2 protease target.Journal of cell science · 2024Article
- Methods and computational tools to study eukaryotic cell migrationFrontiers in cell and developmental biology · 2024Review
- Revisiting the calpain hypothesis of learning and memory 40 years later.Frontiers in molecular neuroscience · 2024Review
- Calpain Regulation and Dysregulation-Its Effects on the Intercalated Disk.International journal of molecular sciences · 2023Review
- Organotypic 3D Co-Culture of Human Pleura as a Novel In Vitro Model ofBioengineering (Basel, Switzerland) · 2023Article
- The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential.EMBO reports · 2023Article
- Static magnetic field regulates proliferation, migration, and differentiation of human dental pulp stem cells by MAPK pathway.Cytotechnology · 2022Article
- Metastasis and MAPK Pathways.International journal of molecular sciences · 2022Review
- LRP-1-dependent control of calpain expression and activity: A new mechanism regulating thyroid carcinoma cell adhesion.Frontiers in oncology · 2022Article
- The role of calcium-calpain pathway in hyperthermia.Frontiers in molecular medicine · 2022Review
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
- Review
- MicroRNA-137 Inhibited Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting Calpain-2.BioMed research international · 2021Article
65 more citing papers are in PubMed but not listed here.
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 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How m-calpain is activated in cells has challenged investigators because in vitro activation requires near-millimolar calcium. Previously, we demonstrated that m-calpain activation by growth factors requires extracellular signal-regulated kinase (ERK); this enables tail deadhesion and allows productive motility. We now show that ERK directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (EGF)-induced calpain activation in vitro and in vivo. Replacing the serine with alanine limits activation by EGF and subsequent cell deadhesion and motility. A construct with the serine converted to glutamic acid displays constitutive activity in vivo; expression of an estrogen receptor fusion construct produces a tamoxifen-sensitive enzyme. Interestingly, EGF-induced m-calpain activation occurs in the absence of increased intracellular calcium levels; EGF triggers calpain even in the presence of intracellular calcium chelators and in calcium-free media. These data provide evidence that m-calpain can be activated through the ERK cascade via direct phosphorylation and that this activation may occur in the absence of cytosolic calcium fluxes.
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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.