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Cited by 145Cytokine Signaling Pathways and Interactionsinterferon and immune responsesReceptor Mechanisms and Signaling

Ligand-Induced Assembly and Activation of the Gamma Interferon Receptor in Intact Cells

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Bach, Erika A., Tanner, J. William, Marsters, Scot, Ashkenazi, Avi, Aguet, Michel, Shaw, Andrey S., Schreiber, Robert D.·1996·Molecular and Cellular Biology
DOI 10.1128/mcb.16.6.3214PMC PMC231315
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Abstract

Functionally active gamma interferon (IFN-gamma) receptors consist of an alpha subunit required for ligand binding and signal transduction and a beta subunit required primarily for signaling. Although the receptor alpha chain has been well characterized, little is known about the specific role of the receptor beta chain in IFN-gamma signaling. Expression of the wild-type human IFN-gamma receptor beta chain in murine L cells that stably express the human IFN-gamma receptor alpha chain (L.hgR) produced a murine cell line (L.hgR.myc beta) that responded to human IFN-gamma. Mutagenesis of the receptor beta-chain intracellular domain revealed that only two closely spaced, membrane-proximal sequences (P263PSIP267 and I270EEYL274) are required for function. Coprecipitation studies showed that these sequences are necessary for the specific and constitutive association of the receptor beta chain with the JAK-2 tyrosine kinase. These experiments also revealed that the IFN-gamma receptor alpha and beta chains are not preassociated on the surface of unstimulated cells but rather are induced to associate in an IFN-gamma-dependent fashion. A chimeric protein in which the intracellular domain of the beta chain was replaced by JAK-2 complemented human IFN-gamma signaling and biologic responsiveness in L.hgR. In contrast, a c-src-containing beta-chain chimera did not. These results indicate that the sole obligate role of the IFN-gamma receptor beta chain in signaling is to recruit JAK-2 into the ligand-assembled receptor complex.

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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 [8]

    The paper’s main-text excerpt (passage [5]; section and page not supplied) links IFNγ receptor signaling to JAK2 recruitment, supporting the IFNγ–JAK2 part of the cited statement. It does not establish IL-6 activation of JAK2. The citations attached to JAK1, STAT1, and STAT3 in the citing sentence are separate from this source’s citation to JAK2. (LLM, conf=0.85)

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Research works printed but not linked: 32

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Authors
Bach, E. A., Tanner, J. W., Marsters, S., Ashkenazi, A., Aguet, M., Shaw, A. S., & Schreiber, R. D.
Affiliations
  • Washington University in St. Louis (US)
  • Genentech (US)
  • Center for Immunology, Department of Pathology, Washington University School of Medicine
Corresponding author
Schreiber, Robert D.
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
1996-06
Volume
16
Issue
6
Pages
3214-3221
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.16.6.3214
PMC
PMC231315
OpenAlex
W2161538693
Cited by
145
References
0
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2016: 3 · 2015: 2 · 2013: 2 · 2012: 8
FWCI
6.00
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health
  • 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 signaling, receptor assembly, cytoplasmic domain, chimeric receptors, Src kinase, signal transduction, L cells
MeSH terms
Interferon gamma Receptor, Amino Acid Sequence, Animals, Binding Sites, Humans, Interferon-gamma, L Cells, Ligands, Models, Biological, Molecular Sequence Data, Protein Conformation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Recombinant Proteins, Signal Transduction, Antigens, CD, Mutagenesis, Site-Directed, Receptors, Interferon, Mice, Janus Kinase 2

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