Journal article
Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: identification of the active components and JAK2 and gp130 as substrates
Nadia J Kershaw, Artem Laktyushin, Nicos A Nicola, Jeffrey J Babon
GROWTH FACTORS | INFORMA HEALTHCARE | Published : 2014
Abstract
SOCS3 (suppressor of cytokine signaling 3) inhibits the intracellular signaling cascade initiated by exposure of cells to cytokines. SOCS3 regulates signaling via two distinct mechanisms: directly inhibiting the catalytic activity of Janus kinases (JAKs) that initiate the intracellular signaling cascade and catalysing the ubiquitination of signaling components by recruiting components of an E3 ubiquitin ligase complex. Here we investigate the latter mode-of-action biochemically by reconstructing a SOCS3-based E3 ubiquitin ligase complex in vitro using fully purified, recombinant components and examining its ability to promote the ubiquitination of molecules involved in the cytokine signaling..
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Funding Acknowledgements
N.A.N. acknowledges fellowship support from the National Health and Medical Research Council and J.J.B. from the Australian Research Council.