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Science 293 (5532): 1136-1138

Copyright © 2001 by the American Association for the Advancement of Science

Cytokine-Specific Transcriptional Regulation Through an IL-5Ralpha Interacting Protein

Niels Geijsen,1 Iain J. Uings,2 Cornelieke Pals,1 John Armstrong,2 Murray McKinnon,2 Jan A. M. Raaijmakers,1 Jan-Willem J. Lammers,1 Leo Koenderman,1 Paul J. Coffer1*

Cytokine receptors consist of multiple subunits, which are often shared between different receptors, resulting in the functional redundancy sometimes observed between cytokines. The interleukin 5 (IL-5) receptor consists of an IL-5-specific alpha -subunit (IL-5Ralpha ) and a signal-transducing beta -subunit (beta c) shared with the IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors. In this study, we sought to find a role for the cytoplasmic domain of IL-5Ralpha . We show that syntenin, a protein containing PSD-95/Discs large/zO-1 (PDZ) domains, associates with the cytoplasmic tail of the IL-5Ralpha . Syntenin was found to directly associate with the transcription factor Sox4. Association of syntenin with IL-5Ralpha was required for IL-5-mediated activation of Sox4. These studies identify a mechanism of transcriptional activation by cytokine-specific receptor subunits.

1 Department of Pulmonary Diseases, Heart Lung Center Utrecht, University Medical Center, G03.550, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
2 Glaxo Wellcome Medicine Research Center, Cell Biology Unit, Gunnels Wood Road, Stevenage, Hertfordshire, SG12NY, UK.
*   To whom correspondence should be addressed. E-mail: P.Coffer{at}

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Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization.
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Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output.
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M. M. Sira, T. Yoshida, M. Takeuchi, Y. Kashiwayama, T. Futatani, H. Kanegane, A. Sasahara, Y. Ito, M. Mizuguchi, T. Imanaka, et al. (2009)
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Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells.
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The ins and outs of syntenin, a multifunctional intracellular adaptor protein.
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Cancer Res. 65, 10901-10911
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J. Hanna, P. Bechtel, Y. Zhai, F. Youssef, K. McLachlan, and O. Mandelboim (2004)
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S. Sannohe, T. Adachi, K. Hamada, K. Honda, Y. Yamada, N. Saito, C-H. Cui, H. Kayaba, K. Ishikawa, and J. Chihara (2003)
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J. Immunol. 170, 5359-5366
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Granulocyte-Macrophage Colony-stimulating Factor Signals for Increased Glucose Transport via Phosphatidylinositol 3-Kinase- and Hydrogen Peroxide-dependent Mechanisms.
M. Dhar-Mascareno, J. Chen, R. H. Zhang, J. M. Carcamo, and D. W. Golde (2003)
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Cloning and Characterization of a Family of Proteins Associated with Mpl.
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