Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 13
The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor
mediates negative regulation of LIF signalling
Thomas Clahsen1, Ute Lehmann1, Claudia Stross1, Heike M. Hermanns1, Rudolf
Volkmer-Engert2, Jens Schneider-Mergener2, Peter C. Heinrich1, Fred Schaper1
1 Department of Biochemistry, RWTH Aachen, Pauwelsstraße 30, D-52074 Aachen,
Germany, E-mail: Thomas.Clahsen@post.rwth-aachen.de
2 Department of Medical Immunology, Universitätsklinikum Charité, Molecular
Libraries and Recognition, Ziegelerstrasse 5-9, Berlin D-10117, Germany
Signalling of interleukin-6 and interleukin-11 through gp130 homodimeric receptor
complexes has been analysed with respect to initiation and termination of signalling in great
detail. Gp130 contains a crucial motif around tyrosine Y759 which mediates negative
regulation through the feedback inhibitor SOCS3 and the protein tyrosine phosphatase SHP2.
Signalling of LIF, CNTF, CT-1, CLC or OSM through gp130/LIF-R is believed to be similar
due to the presence of the common signal transducer gp130 within the receptor complexes
utilized, but the difference in the composition of gp130/gp130-homodimers and gp130/LIF-Rheterodimers
is likely to be reflected in different signalling. Here, we analysed the
contribution of the LIF-R within the gp130/LIF-R complex to negative regulation mediated
by SHP2 and SOCS3. We show that SHP2 contributes to the negative regulation of signalling
through gp130/LIF-R complexes. The inhibitory tyrosine motifs within the cytoplasmic parts
of gp130 and the LIF-R act independently. Whereas SHP2 and SOCS3 bind directly to the
inhibitory motif of gp130, only SHP2 was found to bind to the corresponding inhibitory
sequence of the LIF-R. This observation was further corroborated by experiments indicating
that mainly gp130 contributes to the inhibition of signalling by SOCS3.
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