ArticleThe EMBO journal1992
Conversion of human interleukin-4 into a high affinity antagonist by a single amino acid replacement.
Article in The EMBO journal, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 173 citations in OpenAlex.
- Design of Glycoengineered IL-4 Antagonists Employing Chemical and Biosynthetic Glycosylation.ACS omega · 2023Article
- Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer.Frontiers in immunology · 2020Review
- Targeting IL4/IL4R for the treatment of epithelial cancer metastasis.Clinical & experimental metastasis · 2015Review
- Insights into cytokine-receptor interactions from cytokine engineering.Annual review of immunology · 2015Review
- Multifarious determinants of cytokine receptor signaling specificity.Advances in immunology · 2014Review
- IL-27 structural analysis demonstrates similarities with ciliary neurotrophic factor (CNTF) and leads to the identification of antagonistic variants.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Rational design of interleukin-21 antagonist through selective elimination of the gammaC binding epitope.The Journal of biological chemistry · 2010Article
- The RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis Inactivate the Th2 cytokines interleukin-4 and interleukin-5.Infection and immunity · 2009Article
- Pinellia ternata, Citrus reticulata, and their combinational prescription inhibit eosinophil infiltration and airway hyperresponsiveness by suppressing CCR3+ and Th2 cytokines production in the ovalbumin-induced asthma model.Mediators of inflammation · 2009Article
- A modular interface of IL-4 allows for scalable affinity without affecting specificity for the IL-4 receptor.BMC biology · 2006Article
- Display of passenger proteins on the surface of Escherichia coli K-12 by the enterohemorrhagic E. coli intimin EaeA.Journal of bacteriology · 2001Article
- Immune response induction and new effector mechanisms possibly involved in protection conferred by the Cuban anti-meningococcal BC vaccine.Infection and immunity · 2001Article
- Comparative model building of interleukin-7 using interleukin-4 as a template: a structural hypothesis that displays atypical surface chemistry in helix D important for receptor activation.Protein science : a publication of the Protein Society · 2000Article
- Regulation of cellular 15-lipoxygenase activity on pretranslational, translational, and posttranslational levels.Lipids · 1999Review
- An immune cell-selective interleukin 4 agonist.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Dual effect of interleukin 4 on HIV-1 expression: implications for viral phenotypic switch and disease progression.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Article
- A mixed-charge pair in human interleukin 4 dominates high-affinity interaction with the receptor alpha chain.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Regulation of 15-lipoxygenase expression in lung epithelial cells by interleukin-4.The Biochemical journal · 1996Article
- Detection of elevated levels of IL-4, IL-6, and IL-10 in blister fluid of bullous pemphigoid.Archives of dermatological research · 1996Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-4 (IL-4) represents a prototypic lymphokine (for a recent review see Paul, 1991). It promotes differentiation of B-cells and the proliferation of T- and B-cell, and other cell types of the lymphoid system. An antagonist of human IL-4 was discovered during the studies presented here after Tyr124 of the recombinant protein had been substituted by an aspartic acid residue. This IL-4 variant, Y124D, bound with high affinity to the IL-4 receptor (KD = 310 pM), but retained no detectable proliferative activity for T-cells and inhibited IL-4-dependent T-cell proliferation competitively (K(i) = 620 pM). The loss of efficacy in variant Y124D was estimated to be greater than 100-fold on the basis of a weak partial agonist activity for the very sensitive induction of CD23 positive B-cells. The substitution of Tyr124 by either phenylalanine, histidine, asparagine, lysine or glycine resulted in partial agonist variants with unaltered receptor binding affinity and relatively small deficiencies in efficacy. These results demonstrate that high affinity binding and signal generation can be uncoupled efficiently in a ligand of a receptor belonging to the recently identified hematopoietin receptor family. In addition we show for the first time, that a powerful antagonist acting on the IL-4 receptor system can be derived from the IL-4 protein.
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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.