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Role of the Interleukin (IL)-28 Receptor Tyrosine Residues for Antiviral and Antiproliferative Activity of IL-29/Interferon-λ1
Open accessAbstract
Interferon (IFN)-lambda 1, -lambda 2, and -lambda 3 are the latest members of the class II cytokine family and were shown to have antiviral activity. Their receptor is composed of two chains, interleukin-28R/likely interleukin or cytokine or receptor 2 (IL-28R/LICR2) and IL-10R beta, and mediates the tyrosine phosphorylation of STAT1, STAT2, STAT3, and STAT5. Here, we show that activation of this receptor by IFN-lambda 1 can also inhibit cell proliferation and induce STAT4 phosphorylation, further extending functional similarities with type I IFNs. We used IL-28R/LICR2-mutated receptors to identify the tyrosines required for STAT activation, as well as antiproliferative and antiviral activities. We found that IFN-lambda 1-induced STAT2 tyrosine phosphorylation is mediated through tyrosines 343 and 517 of the receptor, which showed some similarities with tyrosines from type I IFN receptors involved in STAT2 activation. These two tyrosines were also responsible for antiviral and antiproliferative activities of IFN-lambda 1. By contrast, STAT4 phosphorylation (and to some extent STAT3 activation) was independent from IL-28R/LICR2 tyrosine residues. Taken together, these observations extend the functional similarities between IFN-lambdas and type I IFNs and shed some new light on the mechanisms of activation of STAT2 and STAT4 by these cytokines.
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Cites
DUMOUTIER, L., LEJEUNE, D., HOR, S., FICKENSCHER, H., & RENAULD, J.-C. (2003) · Biochemical Journal · doi:10.1042/bj20021935 · Cited by 128
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Duke, G. M., & Palmenberg, A. C. (1989) · Journal of Virology · doi:10.1128/jvi.63.4.1822-1826.1989 · Cited by 120
Cited by
Marcello, T., Grakoui, A., Barba–Spaeth, G., Machlin, E. S., Kotenko, S. V., Macdonald, M. R., & Rice, C. M. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.09.052 · Cited by 561
Self-citationEvolutionary divergence and functions of the human interleukin (IL) gene family
Brocker, C., Thompson, D., Matsumoto, A., Nebert, D. W., & Vasiliou, V. (2010) · Human Genomics · doi:10.1186/1479-7364-5-1-30 · Cited by 368
Impact of aging on dendritic cell functions in humans
Agrawal, A., & Gupta, S. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2010.06.004 · Cited by 246
Interferons: Signaling, antiviral and viral evasion
Bonjardim, C. A., Ferreira, P. C. P., & Kroon, E. G. (2009) · Immunology Letters · doi:10.1016/j.imlet.2008.11.002 · Cited by 196
Sridharan, A., Esposo, M., Kaushal, K., Tay, J., Osann, K., Agrawal, S., Gupta, S., & Agrawal, A. (2011) · AGE · doi:10.1007/s11357-010-9191-3 · Cited by 165
Metadata
- Authors
- Dumoutier, L., Tounsi, A., Michiels, T., Sommereyns, C., Kotenko, S. V., & Renauld, J.-C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 31
- Pages
- 32269-32274
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2083733004
- Cited by
- 291
- References
- 2
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Dumoutier, L., Tounsi, A., Michiels, T., Sommereyns, C., Kotenko, S. V., & Renauld, J.-C. (2004). Role of the Interleukin (IL)-28 Receptor Tyrosine Residues for Antiviral and Antiproliferative Activity of IL-29/Interferon-λ1. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m404789200
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