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Science 288 (5475): 2357-2360

Copyright © 2000 by the American Association for the Advancement of Science

Cross Talk Between Interferon-gamma and -alpha /beta Signaling Components in Caveolar Membrane Domains

Akinori Takaoka, 1 Yukiko Mitani, 1 Hirofumi Suemori, 2 Mitsuharu Sato, 1 Taeko Yokochi, 1 Shigeru Noguchi, 2 Nobuyuki Tanaka, 1 Tadatsugu Taniguchi 1*

Definition of cellular responses to cytokines often involves cross-communication through their respective receptors. Here, signaling by interferon-gamma (IFN-gamma ) is shown to depend on the IFN-alpha /beta receptor components. Although these IFNs transmit signals through distinct receptor complexes, the IFN-alpha /beta receptor component, IFNAR1, facilitates efficient assembly of IFN-gamma -activated transcription factors. This cross talk is contingent on a constitutive subthreshold IFN-alpha /beta 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.

1 Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
2 Meiji Institute of Health Science, Meiji Milk Products, Naruda 540, Odawara-shi, Kanagawa 250-0862, Japan.
*   To whom correspondence should be addressed. E-mail: tada{at}m.u-tokyo.ac.jp

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