Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 30
A role for Src and receptor tyrosine kinases but not for Janus kinases in SOCS3 tyrosine
phosphorylation
Ulrike Sommer1, Christine Schmid1, Radoslaw M. Sobota1, Ute Lehmann1, James A.
Johnston2, Fred Schaper1, Peter C. Heinrich1 and Serge Haan1
1 Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen,
Pauwelsstrasse 30, D-52074 Aachen, Germany
2 Dept. Immunology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL,
Northern Ireland
The suppressors of cytokine signalling (SOCS) are negative feedback inhibitors of cytokine
signal transduction. SOCS3 is a key negative regulator of 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 signalling. Tyrosine phosphorylated SOCS3
was detected upon treatment of mouse embryonic fibroblasts (MEF) with IL 6. Interestingly,
the observed SOCS3 phosphorylation does not require SOCS3 recruitment to phosphotyrosine
pY759 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 MEF
cells, 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 (RTKs) such as PDGFR or EGFR can very potently
phosphorylate IL-6 induced SOCS3. Taken together, these results suggest that SOCS3
phosphorylation is not a JAK-mediated phenomenom but is dependent on the activity of other
kinases such as Src kinases or RTKs which can either be constitutively active or activated by
an additional stimulus.
This work has been supported by the Deutsche Forschungsgemeinschaft (HA3433/3) and the
Fonds der Chemischen Industrie (Frankfurt am Main, Germany).
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