Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130.
- S. Nicholson, D. D. De Souza, M. Baca
- BiologyProceedings of the National Academy of Sciences…
- 6 June 2000
Data suggest that the mechanism by which SOCS-3 inhibited signaling in cells transfected with a chimeric receptor containing the wild-type gp130 intracellular domain depends on recruitment to the phosphorylated gp130 receptor, and that some of the negative regulatory roles previously attributed to the tyrosine phosphatase SHP-2 might in fact be caused by the action of SOCS.
The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation.
- J. G. Zhang, A. Farley, M. Baca
- BiologyProceedings of the National Academy of Sciences…
- 2 March 1999
It appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway, analogous to the family of F-box-containing proteins.
Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL‐6 signal transduction
- S. Nicholson, T. Willson, N. Nicola
- BiologyEMBO Journal
- 15 January 1999
Although inhibition of signaling by SOCs‐1 and SOCS‐3 requires both the SH2 and N‐terminal domains, their mechanisms of action appear to be biochemically different.
The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability.
- J. Babon, Edward J Mcmanus, R. Norton
- BiologyMolecules and Cells
- 21 April 2006
SOCS-6 Binds to Insulin Receptor Substrate 4, and Mice Lacking the SOCS-6 Gene Exhibit Mild Growth Retardation
- D. Krebs, Rachel T. Uren, W. Alexander
- BiologyMolecular and Cellular Biology
- 1 July 2002
SOCS-6 binds to elongins B and C through its SOCS box, suggesting that it might act as an E3 ubiquitin ligase that targets proteins bound to its SH2 domain for ubiquitination and proteasomal degradation.
Biological Evidence That SOCS-2 Can Act Either as an Enhancer or Suppressor of Growth Hormone Signaling*
- C. Greenhalgh, D. Metcalf, D. Hilton
- BiologyJournal of Biological Chemistry
- 25 October 2002
The generation of SOCS-2-deficient mice, which grow to one and a half times the size of their wild-type littermates, suggests that SOCs-2 may attenuate growth hormone (GH) signaling in vivo, and in vitro studies indicate that, while SOCS -2 can inhibit GH action at low concentrations, at higher concentrations it may potentiate signaling.
Antibody Humanization Using Monovalent Phage Display*
- M. Baca, L. Presta, S. O’Connor, J. Wells
- BiologyJournal of Biological Chemistry
- 18 April 1997
This method provides a general means of rapidly selecting framework mutations that improve the binding of humanized antibodies to their cognate antigens and may prove an attractive alternative to current methods of framework optimization based on cycles of site-directed mutagenesis.
Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction
- W. Alexander, R. Starr, D. Hilton
- BiologyJournal of Leukocyte Biology
- 1 October 1999
It is proposed that the absence of SOCS‐1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.
Chopper, a New Death Domain of the p75 Neurotrophin Receptor That Mediates Rapid Neuronal Cell Death*
- E. Coulson, K. Reid, P. Bartlett
- BiologyJournal of Biological Chemistry
- 29 September 2000
The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75NTR) has been found to be necessary and sufficient to initiate neural cell death. The region was named “Chopper” to…
SH2 domains from suppressor of cytokine signaling-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities.
- D. D. De Souza, L. Fabri, A. Nash, D. Hilton, N. Nicola, M. Baca
- Biology, ChemistryBiochemistry
- 19 June 2002
To better explore the overlap in ligand binding specificities exhibited by these two signaling regulators, the phosphopeptide binding preferences of the SH2 domains from SOCS-3 and SHP-2 are mapped and the design of phosphopePTide ligands based on the consensus motifs are validated.
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