ArticleProceedings of the National Academy of Sciences of the United States of America2011
Processive phosphorylation of ERK MAP kinase in mammalian cells.
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 95 papers.
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Who cites it
95 citing papers in PubMed.
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- Amino acid-dependent TSC2 dephosphorylation by lysosome-PP2A regulates mTORC1 signaling transduction.Life science alliance · 2025Article
- ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events.Journal of molecular biology · 2025Article
- Kinase signaling cascades: an updated mechanistic landscape.Chemical science · 2025Review
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- Molecular and Biophysical Perspectives on Dormancy Breaking: Lessons from Yeast Spore.Biomolecules · 2025Review
- Real time characterization of the MAPK pathway using native mass spectrometry.Communications biology · 2025Article
- Comprehensive network pharmacology and experimental study to investigate the effect and mechanism of solasonine on breast carcinoma treatment.Cancer cell international · 2025Article
- Molecular dynamics simulations of a multicellular model with cell-cell interactions and Hippo signaling pathway.PLoS computational biology · 2024Article
- Mathematical Modeling and Inference of Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Cell Signaling Pathways.International journal of molecular sciences · 2024Review
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- Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins.Medicina (Kaunas, Lithuania) · 2024Review
- Cytoplasmic fluidization contributes to breaking spore dormancy in fission yeast.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury.International journal of molecular sciences · 2024Review
- Structure-Based De Novo Design for the Discovery of Miniprotein Inhibitors Targeting Oncogenic Mutant BRAF.International journal of molecular sciences · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitogen-activated protein (MAP) kinase pathway is comprised of a three-tiered kinase cascade. The distributive kinetic mechanism of two-site MAP kinase phosphorylation inherently generates a nonlinear switch-like response. However, a linear graded response of MAP kinase has also been observed in mammalian cells, and its molecular mechanism remains unclear. To dissect these input-output behaviors, we quantitatively measured the kinetic parameters involved in the MEK (MAPK/ERK kinase)-ERK MAP kinase signaling module in HeLa cells. Using a numerical analysis based on experimentally determined parameters, we predicted in silico and validated in vivo that ERK is processively phosphorylated in HeLa cells. Finally, we identified molecular crowding as a critical factor that converts distributive phosphorylation into processive phosphorylation. We proposed the term quasi-processive phosphorylation to describe this mode of ERK phosphorylation that is operated under the physiological condition of molecular crowding. The generality of this phenomenon may provide a new paradigm for a diverse set of biochemical reactions including multiple posttranslational modifications.
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