ArticleProceedings of the National Academy of Sciences of the United States of America1998
Regulation of interleukin 4-mediated signaling by naturally occurring dominant negative and attenuated forms of human Stat6.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 63 citations in OpenAlex.
- The JAK-STAT Signaling Pathway in Epilepsy.Current neuropharmacology · 2023Review
- The JAK/STAT signaling pathway: from bench to clinic.Signal transduction and targeted therapy · 2021Review
- Impact of STAT Proteins in Tumor Progress and Therapy Resistance in Advanced and Metastasized Prostate Cancer.Cancers · 2021Review
- Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells.Cells · 2019Article
- Transcriptional down-regulation ofeLife · 2019Article
- Role of STAT3 in Genesis and Progression of Human Malignant Gliomas.Molecular neurobiology · 2017Review
- TGF-β-mediated airway tolerance to allergens induced by peptide-based immunomodulatory mucosal vaccination.Mucosal immunology · 2015Article
- Serine protease inhibition attenuates rIL-12-induced GZMA activity and proinflammatory events by modulating the Th2 profile from estrogen-treated mice.Endocrinology · 2014Article
- Insulin receptor substrate-1/2 mediates IL-4-induced migration of human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2009Article
- STAT5 requires the N-domain to maintain hematopoietic stem cell repopulating function and appropriate lymphoid-myeloid lineage output.Experimental hematology · 2007Article
- Proteolytic processing of Stat6 signaling in mast cells as a negative regulatory mechanism.The Journal of experimental medicine · 2002Article
- A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1alpha gene.The Biochemical journal · 2002Article
- The biology of Stat4 and Stat6.Oncogene · 2000Review
- Consequences of Stat6 deletion on Sis/PDGF- and IL-4-induced proliferation and transcriptional activation in murine fibroblasts.Oncogene · 1999Article
- Insulin-like growth factor I synergizes with interleukin 4 for hematopoietic cell proliferation independent of insulin receptor substrate expression.Molecular and cellular biology · 1999Article
- Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias.American journal of human genetics · 1999Article
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 (IL)-4-mediated nuclear signaling by Stat6 has been implicated in lymphoid cell proliferation and the transcriptional activation of genes encoding major histocompatability complex (MHC) class II molecules and Fc receptors. To investigate IL-4-mediated transcriptional events, we cloned two naturally occurring human Stat6 isoforms, Stat6b and Stat6c, that encoded an NH2-terminal truncation or an SH2 domain deletion, respectively. Stat6 variant mRNAs were differentially expressed in many human tissues. To elucidate the biologic role of each isoform, we examined the consequences of overexpression in IL-4-responsive FDC-P2 cells. Stat6 and Stat6b (to a lesser extent) enhanced DNA synthesis, up-regulated endogenous MHC class II and Fcgamma receptors, and became tyrosine phosphorylated in response to IL-4 stimulation. In contrast, Stat6c, which lacks functionally critical SH2 domain residues, unexpectedly inhibited IL-4-mediated mitogenesis and cell surface antigen expression and was not tyrosine phosphorylated. Although Stat6c only modestly diminished endogenous Stat6 tyrosine phosphorylation, it abolished endogenous Stat6 FcgammaRI and Iepsilon DNA binding activity and FcgammaRI-luciferase reporter transcriptional activation. Our results indicate that the molecular mechanism of inhibition by Stat6c was due to suppression of endogenous Stat6 dimer formation. Thus, Stat6b and Stat6c are naturally occurring attenuated and dominant negative Stat6 variants, respectively, that affect IL-4-mediated biologic responses through differential transcriptional regulation.
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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.