SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation

G. Tannahill, Joanne Elliott, A.C. Barry, L. Hibbert, N.A. Cacalano, James Johnston

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Cytokine responses can be regulated by a family of proteins termed suppressors of cytokine signaling (SOCS) which can inhibit the JAK/STAT pathway in a classical negative-feedback manner. While the SOCS are thought to target signaling intermediates for degradation, relatively little is known about how their turnover is regulated. Unlike other SOCS family members, we find that SOCS2 can enhance interleukin-2 (IL-2)- and IL-3-induced STAT phosphorylation following and potentiate proliferation in response to cytokine stimulation. As a clear mechanism for these effects, we demonstrate that expression of SOCS2 results in marked proteasome-dependent reduction of SOCS3 and SOCS1 protein expression. Furthermore, we provide evidence that this degradation is dependent on the presence of an intact SOCS box and that the loss of SOCS3 is enhanced by coexpression of elongin B/C. This suggests that SOCS2 can bind to SOCS3 and elongin B/C to form an E3 ligase complex resulting in the degradation of SOCS3. Therefore, SOCS2 can enhance cytokine responses by accelerating proteasome-dependent turnover of SOCS3, suggesting a mechanism for the gigantism observed in SOCS2 transgenic mice.
Original languageEnglish
Pages (from-to)9115-9126
Number of pages12
JournalMolecular and Cellular Biology
Volume25(20)
Issue number20
DOIs
Publication statusPublished - Oct 2005

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Interleukin-3
Interleukin-2
Cytokines
Proteasome Endopeptidase Complex
Suppressor of Cytokine Signaling Proteins
Gigantism
Ubiquitin-Protein Ligases
Transgenic Mice
Phosphorylation
elongin

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Tannahill, G., Elliott, J., Barry, A. C., Hibbert, L., Cacalano, N. A., & Johnston, J. (2005). SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation. Molecular and Cellular Biology, 25(20)(20), 9115-9126. https://doi.org/10.1128/MCB.25.20.9115-9126.2005
Tannahill, G. ; Elliott, Joanne ; Barry, A.C. ; Hibbert, L. ; Cacalano, N.A. ; Johnston, James. / SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation. In: Molecular and Cellular Biology. 2005 ; Vol. 25(20), No. 20. pp. 9115-9126.
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Tannahill, G, Elliott, J, Barry, AC, Hibbert, L, Cacalano, NA & Johnston, J 2005, 'SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation', Molecular and Cellular Biology, vol. 25(20), no. 20, pp. 9115-9126. https://doi.org/10.1128/MCB.25.20.9115-9126.2005

SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation. / Tannahill, G.; Elliott, Joanne; Barry, A.C.; Hibbert, L.; Cacalano, N.A.; Johnston, James.

In: Molecular and Cellular Biology, Vol. 25(20), No. 20, 10.2005, p. 9115-9126.

Research output: Contribution to journalArticle

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AU - Elliott, Joanne

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AU - Cacalano, N.A.

AU - Johnston, James

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