Suppressor of Cytokine Signaling (SOCS) 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-1
| Autor: | Indu R. Chandrashekaran, Alex N. Bullock, Raymond S. Norton, Andrew I. Webb, Jeffrey J. Babon, Tatiana B. Kolesnik, Sandra E. Nicholson, James M. Murphy, Edmond M. Linossi, Nicos A. Nicola, Lukasz Kedzierski, Tracy A. Willson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Phosphopeptides
Proteomics lcsh:Medicine Suppressor of Cytokine Signaling Proteins Signal transduction Biochemistry Substrate Specificity Mice 0302 clinical medicine Molecular cell biology SOCS5 SOCS6 SOCS3 Phosphorylation Biomacromolecule-Ligand Interactions lcsh:Science 0303 health sciences Multidisciplinary Immune System Proteins Janus kinase 1 Signaling cascades Recombinant Proteins Cell biology Enzymes Tyrosine kinase 2 030220 oncology & carcinogenesis Cytokines Intercellular Signaling Peptides and Proteins Shc Signaling Adaptor Proteins Research Article Src Homology 2 Domain-Containing Transforming Protein 1 MAPK signaling cascades Genetic Vectors Signaling in cellular processes Biology Suppressor of cytokine signalling src Homology Domains Enzyme Regulation 03 medical and health sciences Growth Factors Animals Humans Protein Interactions 030304 developmental biology TYK2 Kinase STAT signaling family Binding Sites Suppressor of cytokine signaling 1 lcsh:R Janus Kinase 3 Proteins Janus Kinase 1 Janus Kinase 2 Surface Plasmon Resonance Protein Structure Tertiary HEK293 Cells Cancer research lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 8, p e70536 (2013) |
| Popis: | Suppressor of Cytokine Signaling (SOCS)5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF) signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR). Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling. |
| Databáze: | OpenAIRE |
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