Mechanisms of SOCS3 phosphorylation upon interleukin-6 stimulation: Contributions of Src- and receptor-tyrosine kinases
Item Type:Journal Article
Citation:Sommer, U, Schmid, C, Sobota, R M, Lehmann, U, Stevenson, N J, Johnston, J A, Schaper, F, Heinrich, P C, Haan, S. Mechanisms of SOCS3 phosphorylation upon interleukin-6 stimulation: Contributions of Src- and receptor-tyrosine kinases, Journal of Biological Chemistry, 280, 36, 2005, 31478-31488
The suppressors of cytokine signaling (SOCS) are negative feedback inhibitors of cytokine signal transduction. SOCS3 is a key negative regulator of interleuking-6 (IL-6) signal transduction. Furthermore, SOCS3 was shown to be phosphorylated upon treatment of cells with IL-2, and this has been reported to regulate its function and half-life. We set out to investigate whether SOCS3 phosphorylation may play a role in IL-6 signaling. Tyrosine-phosphorylated SOCS3 was detected upon treatment of mouse embryonic fibroblasts with IL-6. Interestingly, the observed SOCS3 phosphorylation does not require SOCS3 recruitment to phosphotyrosine (Tyr(P)) 759 of gp130, and the kinetics of SOCS3 phosphorylation do not match the activation kinetics of the Janus kinases. This suggests that other kinases may be involved in SOCS3 phosphorylation. Using Src and Janus kinase inhibitors as well as Src kinase-deficient mouse embryonic fibroblasts, we provide evidence that Src kinases, which we found to be constitutively active in these cells, are involved in the phosphorylation of IL-6-induced SOCS3. In addition, we found that receptor-tyrosine kinases such as platelet-derived growth factor receptor or epidermal growth factor receptor can very potently phosphorylate IL-6-induced SOCS3. Taken together, these results suggest that SOCS3 phosphorylation is not a JAK-mediated phenomenon but is dependent on the activity of other kinases such as Src kinases or receptor-tyrosine kinases, which can either be constitutively active or activated by an additional stimulus.
Description:PUBLISHED: This research was originally published in the Journal of Biological Chemistry. Ulrike Sommer, Christine Schmid, Radoslaw M. Sobota, Ute Lehmann, Nigel J. Stevenson, James A. Johnston, Fred Schaper, Peter C. Heinrich, and Serge Haan. Mechanisms of SOCS3 Phosphorylation upon Interleukin-6 Stimulation. Contributions of Src- and receptor-tyrosine kinases. J. Biol. Chem. 2005; 280:31478-31488. © the American Society for Biochemistry and Molecular Biology or © the Author(s).
Author: Stevenson, Nigel
Publisher:American Society for Biochemistry and Molecular Biology
Type of material:Journal Article
Series/Report no:Journal of Biological Chemistry;
Availability:Full text available
Subject (TCD):Immunology, Inflammation & Infection