DOI: 10.1126/science.288.5475.2357. Cross Talk Between Interferon-γ and -α/β Signaling Components in Caveolar Membrane Domains

Cross Talk Between Interferon-γ and -α/β Signaling Components in Caveolar Membrane Domains

10.1126/science.288.5475.2357

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Definition of cellular responses to cytokines often involves cross-communication through their respective receptors. Here, signaling by interferon-γ (IFN-γ) is shown to depend on the IFN-α/β receptor components. Although these IFNs transmit signals through distinct receptor complexes, the IFN-α/β receptor component, IFNAR1, facilitates efficient assembly of IFN-γ–activated transcription factors. This cross talk is contingent on a constitutive subthreshold IFN-α/β signaling and the association between the two nonligand-binding receptor components, IFNAR1 and IFNGR2, in the caveolar membrane domains. This aspect of signaling cross talk by IFNs may apply to other cytokines.

Bibliography

Takaoka, A., Mitani, Y., Suemori, H., Sato, M., Yokochi, T., Noguchi, S., Tanaka, N., & Taniguchi, T. (2000). Cross Talk Between Interferon-Î³ and -Î±/Î² Signaling Components in Caveolar Membrane Domains. Science, 288(5475), 2357â2360.

Authors 8

Akinori Takaoka (first)
Yukiko Mitani (additional)
Hirofumi Suemori (additional)
Mitsuharu Sato (additional)
Taeko Yokochi (additional)
Shigeru Noguchi (additional)
Nobuyuki Tanaka (additional)
Tadatsugu Taniguchi (additional)

References 47 Referenced 261

10.1016/S0079-6603(08)60026-4
E. DeMaeyer and J. DeMaeyer-Guignard Interferons and Other Regulatory Cytokines (Wiley New York 1988).
J. Vilcek and G. S. Sen in Fields Virology D. M. Fields P. M. Knipe P. M. Howley Eds. (Lippincott-Raven Philadelphia ed. 3 1996) p. 375.
10.1146/annurev.bi.56.070187.003455
10.1016/S0065-2776(08)60428-9
10.1146/annurev.bi.64.070195.003201
10.1146/annurev.immunol.15.1.563
10.1146/annurev.biochem.67.1.227
10.1126/science.8197455
10.1016/S0168-9525(00)89000-9
10.1016/1359-6101(96)00005-6
The result of the antiviral assay presented in figure 2A of U. Müller et al. [ Science 264 1918 (1994)] is consistent with our present results. To investigate further the extent to which the loss of IFNAR1 affects IFN-γ–induced gene expression we examined the mRNA induction kinetics for IRF - 1 and 2′ 5′OAS genes by IFN-γ in the WT and IFNAR1-null MEFs. The induction of IRF-1 mRNA by IFN-γ was six times lower in the mutant MEFs than in the WT MEFs. We also examined the induction of 2′ 5′OAS mRNA which is dependent on ISGF3 in the WT and IFNAR1-null MEFs. The induction of 2′ 5′OAS mRNA by IFN-γ remained undetectable in IFNAR1-null MEFs throughout the time course tested (19).
S. Huang et al. Science 259 1742 (1993). (10.1126/science.8456301)
IFNAR1-deficient and IFNGR1-deficient mice were purchased from B&K Universal Group (North Humberside UK). MEFs and splenocytes were prepared according to standard methods [
10.1093/emboj/18.9.2480
]. Recombinant murine IFN-γ was purchased from Genzyme/Techne.
Flow cytometry and immunoblot analyses revealed that the expression levels of IFNGR1 and IFNGR2 in these cells are essentially the same as in the WT MEFs. Immunoblot analysis showed that nearly the same amount of endogenous Stat1 protein was detected in the WT and IFNAR1-null MEFs.
A. Takaoka and Y. Mitani unpublished data.
M. Matsumoto et al. Biol. Chem. 380 699 (1999). (10.1515/BC.1999.087)
T. Kimura et al. Genes Cells 1 115 (1996). (10.1046/j.1365-2443.1996.08008.x)
Supplemental Web material is available at Science Online at www.sciencemag.org/feature/data/1049334.shl.
M. Sato unpublished results.
L. Erlandsson et al. Curr. Biol. 8 223 (1998). (10.1016/S0960-9822(98)70086-7)
K. Shuai et al. Cell 76 821 (1994). (10.1016/0092-8674(94)90357-3)
10.1128/MCB.17.4.2048
H. Yan et al. EMBO J. 15 1064 (1996). (10.1002/j.1460-2075.1996.tb00444.x)
10.1002/j.1460-2075.1994.tb06422.x
10.1128/iai.26.1.248-253.1979
10.1128/jvi.7.6.792-801.1971
10.1038/42408
10.1016/S1074-7613(00)80577-4
Detergent-free caveolae fractions were prepared as described [
10.1073/pnas.92.22.10104
10.1074/jbc.271.20.11930
]. The reversibility of the effects of filipin treatment was investigated as described [
10.1083/jcb.127.5.1217
10.1016/S1074-7613(00)80577-4
]. Briefly MEFs treated with filipin (Sigma) for 10 min were washed incubated for 60 min in Dulbecco's modified Eagle's medium containing 20% fetal calf serum and then stimulated with IFN-γ.
M. Sato et al. FEBS Lett. 441 106 (1998). (10.1016/S0014-5793(98)01514-2)
A. Takaoka et al. EMBO J. 18 2480 (1999). (10.1093/emboj/18.9.2480)
Preparation of whole-cell extracts binding reactions and gel electrophoresis were done as described [
10.1093/emboj/18.9.2480
]. Unless otherwise noted cells were treated with IFN-γ (250 U/ml) for 30 min. Equal amounts of proteins from whole-cell extracts were loaded onto each lane. Experiments were done in triplicate and were performed separately with at least two independent clones of MEFs derived from the same littermates of the WT or mutant mice.
After the treatment with IFN-γ (250 U/ml) for 15 min cell lysis immunoprecipitation and immunoblotting were done as described [
10.1093/emboj/18.9.2480
]. The following antibodies were purchased: anti-phosphotyrosine anti-Jak1 and anti-Jak2 (Upstate Biotechnology); anti-Stat1 p84/p91 and anti-Stat2 (Santa Cruz); anti-phosphorylated Stat1 (Tyr 701 ) (New England BioLabs); anti-IFNAR1 anti-IFNGR1 and anti-IFNGR2 (Research Diagnostics); and anti-caveolin (Transduction Laboratories).
We thank G. Uzé for the murine IFNAR1 cDNA (GenBank accession number ); J. Vilcek and E. L. Barsoumian for invaluable advice; M. Asagiri N. Hata Y. Kato and S. H. Kim for technical support; Sumitomo Pharmaceuticals for purified murine IFN-α; and Toray Industries for recombinant murine IFN-β. Animal care was in accordance with institutional guidelines of the University of Tokyo. Supported by grants from the Research for the Future Program (96L00307) Yamanouchi Foundation for Research on Metabolic Disorders the Japan Society for the Promotion of Science Advanced Research on Cancer and the Human Frontier Science Program Organization.

Dates

Type	When
Created	23 years ago (July 27, 2002, 5:37 a.m.)
Deposited	1 year, 7 months ago (Jan. 13, 2024, 5:16 a.m.)
Indexed	1 hour, 35 minutes ago (Aug. 24, 2025, 9:06 p.m.)
Issued	25 years, 1 month ago (June 30, 2000)
Published	25 years, 1 month ago (June 30, 2000)
Published Print	25 years, 1 month ago (June 30, 2000)

Funders 0

None

BibTeX

@article{Takaoka_2000, title={Cross Talk Between Interferon-γ and -α/β Signaling Components in Caveolar Membrane Domains}, volume={288}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.288.5475.2357}, DOI={10.1126/science.288.5475.2357}, number={5475}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Takaoka, Akinori and Mitani, Yukiko and Suemori, Hirofumi and Sato, Mitsuharu and Yokochi, Taeko and Noguchi, Shigeru and Tanaka, Nobuyuki and Taniguchi, Tadatsugu}, year={2000}, month=jun, pages={2357–2360} }

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