Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotations Inferred by Curator (IC) using at least one Inferred by Sequence Similarity (ISS) annotation to support the inference
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities
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Original cloning and characterization of human IL-4 as a secreted cytokine with B cell and T cell stimulating activities.
"Supernatant of COS-7 monkey cells transfected with the human cDNA clone stimulated proliferation of human helper T-cell clones and of anti-IgM-activated human B cells, two properties of mouse BSF-1 on mouse cells"
Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface
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Crystal structure at 2.30 angstroms reveals the IL-4/IL4RA binding interface and demonstrates direct ligand-receptor interaction.
"The crystal structure of the intermediate complex between human IL-4 and IL4-BP was determined at 2.3 A resolution. It reveals a novel spatial orientation of the two proteins, a small but unexpected conformational change in the receptor-bound IL-4, and an interface with three separate clusters of trans-interacting residues"
The distinct roles of T cell-derived cytokines and a novel follicular dendritic cell-signaling molecule 8D6 in germinal center-B cell differentiation.
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Characterization of IL-4 receptor binding, growth factor activity, and role in B cell differentiation and isotype switching.
"IL-4 directs GC-B cells to differentiate into memory B cells, whereas IL-10 steers them into PC"
[Inflammatory cytokines (IL-4, IL-5 and IL-13)].
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Documents IL-4 role in type 2 immune responses.
"Th2 cytokines, such as IL-4, IL-5 and IL-13, are pivotal in regulating the allergic phenotype, the IgE response or the inflammatory cell-mediated function"
Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma.
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IL-4 and IL-13 decrease lung epithelial barrier function and wound healing, inhibiting epithelial cell migration on collagen substrates.
"In wound-healing assays of cells grown on collagen I, IL-4 and IL-13 decreased migration, whereas IFN-gamma treatment enhanced migration, compared with control cells"
Interleukin-4 regulates connective tissue growth factor expression in human lung fibroblasts.
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IL-4 attenuates TGF-beta-stimulated CTGF expression in lung fibroblasts by interfering with TGF-beta-induced transcriptional activation of the CTGF gene.
"IL-4 attenuated the TGF-beta-stimulated induction of CTGF mRNA expression by 50%. This effect was selective because IL-4 did not affect fibronectin or alpha1(I) collagen mRNA expression induced by TGF-beta"
Interleukin-4 deficiency promotes gallstone formation.
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IL-4 deficiency in mice promotes gallstone formation on a fat-enriched diet, suggesting a role for IL-4 in cholesterol metabolism.
"IL-4(-/-) mice had a 100% incidence of gallstones and cholesterol crystals"
Human activation-induced cytidine deaminase is induced by IL-4 and negatively regulated by CD45: implication of CD45 as a Janus kinase phosphatase in antibody diversification
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IL-4 induces AID expression in human B cells via JAK/STAT6 signaling, enhanced by CD40 co-stimulation, and negatively regulated by CD45 JAK phosphatase activity.
"IL-4 was able to induce AID expression in human primary B cells and B cell lines, and IL-4-induced AID expression was further enhanced by CD40 signaling. IL-4-dependent AID induction was inhibited by a dominant-negative STAT6, indicating that IL-4 induced AID expression via the Janus kinase (JAK)/STAT6 signaling pathway"
IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway.
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IL-4 and IL-13 protect porcine endothelial cells from complement-mediated killing and apoptosis via PI3K/Akt pathway activation.
"porcine EC incubated with IL-4 or IL-13, but not with IL-10 or IL-11, became protected from killing by complement and apoptosis induced by TNF-alpha plus cycloheximide"
Galectin-9 induces maturation of human monocyte-derived dendritic cells.
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IL-4 drives myeloid dendritic cell differentiation from monocyte precursors.
"Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a dose-dependent manner, although Gal-9 had no or little effect on differentiation of human monocytes into immature DCs"
B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.
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IL-4 inhibits B7-H4 expression on macrophages, in contrast to IL-6 and IL-10 which stimulate it, relevant to tumor immune evasion.
"granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression"
Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system
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Crystal structure reveals molecular basis for IL-4 signaling through both type I (IL4RA/IL2RG) and type II (IL4RA/IL13RA1) receptor complexes, explaining cytokine receptor pleiotropy.
"Here we present the crystal structures of the complete set of type I (IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes"
CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1.
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Study of CCL5-mediated T cell chemotaxis mechanisms; relevance to IL-4 T cell activation annotation is unclear.
"The multistep, coordinated process of T-cell chemotaxis requires chemokines, and their chemokine receptors, to invoke signaling events to direct cell migration"
LEF-1 negatively controls interleukin-4 expression through a proximal promoter regulatory element.
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LEF-1 is a transcriptional repressor of IL-4 gene expression. IL-4 stimulation downregulates LEF-1 and TCF-1, creating a positive feedback loop that reinforces IL-4 expression.
"Knockdown LEF-1 expression by LEF-1-specific small interfering RNA resulted in an increase in the IL-4 mRNA expression"
IFN-lambda1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells.
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IFN-lambda1 suppresses IL-4-driven Th2 responses by inhibiting GATA3 expression and Th2 cytokine (IL-4, IL-13) production in naive and memory T cells.
"Expression of Th2 cytokines (IL-4 and IL-13) was suppressed in naive and memory CD4(+) T cells by IFN-lambda1, without affecting their proliferation"
Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3
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IL-4 promotes Th2 development by inducing GATA3 expression via STAT6; GATA3 autoregulation maintains Th2 stability; type I IFN can reverse this.
"IL-4 promotes Th2 development by inducing the expression of the GATA3 transcription factor, and the Th2 phenotype is stabilized by a GATA3-dependent autoregulatory loop"
Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions
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Demonstrates IL-4-dependent monocyte-to-dendritic cell differentiation pathways in human embryonic and fetal systems.
"monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions"
Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines.
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Documents IL-4 signaling through JAK-STAT pathway and leukocyte differentiation.
"Formation of the IL-4/IL-4Rα/γc or IL-4/IL-4Rα/IL-13Rα1 complex on the cell surface activates intracellular signaling pathways including the Jak-STAT and the PI3K/Akt pathways"
Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties
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Study focuses on FGFR inhibitors; IL-4/IL4R interaction likely from high-throughput IntAct data associated with this publication.
"we report the pharmacologic characterization of the chemical SSR128129E (SSR), which inhibits fibroblast growth factor receptor (FGFR) signaling by binding to the extracellular FGFR domain without affecting orthosteric FGF binding"
Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat.
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IL-4/IL-13 signaling in macrophages is required for cold-induced beige fat biogenesis. IL-4 administration increases beige fat and ameliorates obesity.
"Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat"
IL-16 regulates macrophage polarization as a target gene of mir-145-3p.
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IL-4 and IL-13 induce M2 macrophage polarization with higher IL-10 and lower pro-inflammatory cytokine expression compared to M1 macrophages.
"THP-1 cells were induced by IL-4 and IL-13 following PMA incubation (M2 polarized macrophages) or induced by IFN-gamma and LPS (M1 classical macrophage activation)"
miR‑320a upregulation contributes to the development of preeclampsia by inhibiting the growth and invasion of trophoblast cells by targeting interleukin 4.
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IL-4 is a direct target of miR-320a in trophoblast cells. IL-4 promotes trophoblast proliferation and invasion, and miR-320a-mediated IL-4 suppression contributes to preeclampsia pathogenesis.
"miR-320a upregulation inhibited the proliferation and invasion of HTR-8/SVneo cells by directly targeting IL-4"
Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4.
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IL-4 modulates monocyte phenotype and function, inducing macrophage-like morphology, MHC class II upregulation, and inhibiting secretion of cytostatic and chemotactic compounds.
"Highly purified peripheral blood monocytes were cultured in the presence of rIL-4"
Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor.
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The IL-2 receptor gamma chain is a functional component of the IL-4 receptor, demonstrated by chemical cross-linking, binding affinity augmentation, and requirement for IL-4-mediated IRS-1 phosphorylation.
"IL-2R gamma was demonstrated to be a component of the IL-4 receptor on the basis of chemical cross-linking data, the ability of IL-2R gamma to augment IL-4 binding affinity, and the requirement for IL-2R gamma in IL-4-mediated phosphorylation of insulin receptor substrate-1"
JAK1 binds IL4R in IL4-bound IL4R1
IL4:IL4R:JAK2 binds IL13RA1:TYK2
p-Y705-STAT3,p-Y641-STAT6 dissociate
IL4:IL4R:JAK2 binds IL2RG:JAK3
JAK1 phosphorylates STAT3,STAT6
IL4R, IL2RG, JAK1 in IL4-bound IL4R1:JAK1 are phosphorylated
STAT3,STAT6 bind p-Y-IL4R