Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling
- 3 February 2005
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 102 (7) , 2328-2333
- https://doi.org/10.1073/pnas.0409675102
Abstract
The suppressors of cytokine signaling (SOCS) proteins are a family of SH2 domain-containing intracellular inhibitors of cytokine signal transduction that act by several different mechanisms. Recent evidence suggests that the action of the SOCS proteins may extend beyond the cytokine receptors to signaling initiated by members of the tyrosine kinase receptor family. In this study, the ability of SOCS-5 to negatively regulate signaling cascades downstream of the epidermal growth factor receptor (EGF-R) has been examined by using an EGF-responsive cell line engineered to constitutively express the EGF-R and SOCS-5 or SOCS-5 mutants. SOCS-5 associated with the EGF-R complex in an EGF-independent manner, and the mitogenic response to EGF of all SOCS-5-expressing cell lines was dramatically inhibited when compared with control cell lines. Furthermore, this effect was abrogated after deletion of the SOCS-5 SOCS box. This result suggests that the inhibition of signaling occurs through enhanced proteasomal degradation of the EGF-R through SOCS box recruitment of E3 ubiquitin ligase activity.Keywords
This publication has 45 references indexed in Scilit:
- Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extensionPublished by Elsevier ,2003
- Identification of Both Positive and Negative Domains within the Epidermal Growth Factor Receptor COOH-terminal Region for Signal Transducer and Activator of Transcription (STAT) ActivationPublished by Elsevier ,2002
- SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing discOncogene, 2002
- Suppressor of Cytokine Signaling (SOCS)-3 Protein Interacts with the Insulin-like Growth Factor-I ReceptorBiochemical and Biophysical Research Communications, 2000
- The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat familiesGenes & Development, 1998
- JAKS AND STATS: Biological ImplicationsAnnual Review of Immunology, 1998
- A Novel Ligand for an SH3 Domain of the Adaptor Protein Nck Bears an SH2 Domain and Nuclear Signaling MotifsBiochemical and Biophysical Research Communications, 1997
- IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: Demonstration of a novel role for c-mycCell, 1992
- Binding, Internalization, and Degradation of125I-Multipotential Colony-Stimulating Factor (Interleukin-3) By FDCP-1 CellsGrowth Factors, 1988
- Cellular Processing of Murine Colony-Stimulating Factor (Multi-CSF, GM-CSF, G-CSF) Receptors by Normal Hemopoietic Cells and Cell LinesGrowth Factors, 1988