ArticleFree radical biology & medicine2012
Identification of a redox-sensitive switch within the JAK2 catalytic domain.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Nitration in cancer signaling.Redox biology · 2026Review
- A druggable redox switch on SHP1 controls macrophage inflammation.Nature chemical biology · 2026Article
- A druggable redox switch on SHP1 controls macrophage inflammation.bioRxiv : the preprint server for biology · 2026Article
- From Coffee Alkaloid to Ovarian Targets: An Integrated Computational Framework for Trigonelline in Ovarian Aging.Food science & nutrition · 2026Article
- Revisiting ROS: duality in organ aging progression.Molecular biology reports · 2025Review
- Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Redox regulation of tyrosine kinase signalling: more than meets the eye.Journal of biochemistry · 2020Review
- The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia.International journal of molecular sciences · 2019Review
- Organic dust induces inflammatory gene expression in lung epithelial cells via ROS-dependent STAT-3 activation.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications.Oxidative medicine and cellular longevity · 2018Review
- Reactive Oxygen Species as Intracellular Signaling Molecules in the Cardiovascular System.Current cardiology reviews · 2018Review
- Humanin analogue, S14G-humanin, has neuroprotective effects against oxygen glucose deprivation/reoxygenation by reactivating Jak2/Stat3 signaling through the PI3K/AKT pathway.Experimental and therapeutic medicine · 2017Article
- Cysteines as Redox Molecular Switches and Targets of Disease.Frontiers in molecular neuroscience · 2017Review
- Biological chemistry and functionality of protein sulfenic acids and related thiol modifications.Free radical research · 2016Review
- Dynamic Redox Regulation of IL-4 Signaling.PLoS computational biology · 2015Article
- Oxidative metabolism in cancer: A STAT affair?JAK-STAT · 2013Review
- Redox regulation of Janus kinase: The elephant in the room.JAK-STAT · 2013Review
- The redox biochemistry of protein sulfenylation and sulfinylation.The Journal of biological chemistry · 2013Review
- Article
- Depletion of cellular glutathione modulates LIF-induced JAK1-STAT3 signaling in cardiac myocytes.The international journal of biochemistry & cell biology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Four cysteine residues (Cys866, Cys917, Cys1094, and Cys1105) have direct roles in cooperatively regulating Janus kinase 2 (JAK2) catalytic activity. Additional site-directed mutagenesis experiments now provide evidence that two of these residues (Cys866 and Cys917) act together as a redox-sensitive switch, allowing JAK2's catalytic activity to be directly regulated by the redox state of the cell. We created several variants of the truncated JAK2 (GST/(NΔ661)rJAK2), which incorporated cysteine-to-serine or cysteine-to-alanine mutations. The catalytic activities of these mutant enzymes were evaluated by in vitro autokinase assays and by in situ autophosphorylation and transphosphorylation assays. Cysteine-to-alanine mutagenesis revealed that the mechanistic role of Cys866 and Cys917 is functionally distinct from that of Cys1094 and Cys1105. Most notable is the observation that the robust activity of the CC866,917AA mutant is unaltered by pretreatment with dithiothreitol or o-iodosobenzoate, unlike all other JAK2 variants previously examined. This work provides the first direct evidence for a cysteine-based redox-sensitive switch that regulates JAK2 catalytic activity. The presence of this redox-sensitive switch predicts that reactive oxygen species can impair the cell's response to JAK-coupled cytokines under conditions of oxidative stress, which we confirm in a murine pancreatic β-islet cell line.
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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.