Ligand‐induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91).
Open accessAbstract
Herein we report that interferon-gamma (IFN gamma) induces the rapid and reversible tyrosine phosphorylation of the IFN gamma receptor. Using a panel of receptor intracellular domain mutants, we show that a membrane-proximal LPKS sequence (residues 266-269) is required for ligand-induced tyrosine kinase activation and/or kinase-receptor association and biological responsiveness, and a functionally critical membrane-distal tyrosine residue (Y440) is a target of the activated enzyme. The biological significance of Y440 phosphorylation was demonstrated by showing that a receptor-derived nonapeptide corresponding to receptor residues 436-444 and containing phosphorylated Y440 bound specifically to p91, blocked p91 phosphorylation and inhibited the generation of an active p91-containing transcription factor complex. In contrast, nonphosphorylated wild-type, phosphorylated mutant, or phosphorylated irrelevant peptides did not. Moreover, the phosphorylated Y440-containing peptide did not interact with a related but distinct latent transcription factor (p113) which is activatible by IFN alpha but not IFN gamma. These results thus document the specific and inducible association of p91 with the phosphorylated IFN gamma receptor and thereby elucidate the mechanism by which ligand couples the IFN gamma receptor to its signal transduction system.
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Both IFNγ and IL-6 can activate JAK1 and JAK2, and subsequently STAT1 and STAT3.
“Both IFN␥ and IL-6 can activate JAK1 (4 -6) and JAK2 (7-10), and subsequently STAT1 (11,12) and STAT3 (6,13,14).”
From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [5]
The Discussion reports that IFNγ rapidly activates JAK1 and JAK2, and the section on Y440 phosphorylation reports IFNγ-induced activation of p91. The paper mentions IL-6 receptor phosphorylation but does not establish that IL-6 activates JAK1, JAK2, STAT1, or STAT3; it also does not report STAT3 activation by IFNγ. (LLM, conf=0.86)
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Research works printed but not linked: 11
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- Authors
- Greenlund, A. C., Farrar, M. A., Viviano, B. L., & Schreiber, R. D.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- The EMBO Journal
- Published
- 1994-04-01
- Volume
- 13
- Issue
- 7
- Pages
- 1591-1600
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC394989
- OpenAlex
- W135486017
- Cited by
- 454
- References
- 0
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 7 · 2018: 7 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 8 · 2012: 10
- FWCI
- 23.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universität Zürich
- U.S. Public Health Service
- National Cancer Institute (CA-43059)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- interferon-gamma receptor, tyrosine phosphorylation, signal transduction, receptor tyrosine kinase, transcription factor complex
- MeSH terms
- Interferon gamma Receptor, Amino Acid Sequence, Animals, Base Sequence, Chromosomes, Human, Pair 21, Enzyme Activation, Humans, Interferon-gamma, Ligands, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Species Specificity, Structure-Activity Relationship, Transcription Factors, Signal Transduction, Receptors, Interferon, Mice
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