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Type: Journal article
Title: A family of cytokine-inducible inhibitors of signalling.
Author: Starr, R.
Willson, T.
Viney, E.
Murray, L.
Rayner, J.
Jenkins, B.
Gonda, T.
Alexander, W.
Metcalf, D.
Nicola, N.
Hilton, D.
Citation: Nature, 1997; 387(6636):917-921
Issue Date: 1997
ISSN: 0028-0836
Statement of
Robyn Starr, Tracy A. Willson, Elizabeth M. Viney, Leecia J. L. Murray, John R. Rayner, Brendan J. Jenkins, Thomas J. Gonda, Warren S. Alexander, Donald Metcalf, Nicos A. Nicola and Douglas J. Hilton
Abstract: Cytokines are secreted proteins that regulate important cellular responses such as proliferation and differentiation. Key events in cytokine signal transduction are well defined: cytokines induce receptor aggregation, leading to activation of members of the JAK family of cytoplasmic tyrosine kinases. In turn, members of the STAT family of transcription factors are phosphorylated, dimerize and increase the transcription of genes with STAT recognition sites in their promoters. Less is known of how cytokine signal transduction is switched off. We have cloned a complementary DNA encoding a protein SOCS-1, containing an SH2-domain, by its ability to inhibit the macrophage differentiation of M1 cells in response to interleukin-6. Expression of SOCS-1 inhibited both interleukin-6-induced receptor phosphorylation and STAT activation. We have also cloned two relatives of SOCS-1, named SOCS-2 and SOCS-3, which together with the previously described CIS form a new family of proteins. Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction.
Keywords: Tumor Cells, Cultured
Mice, Inbred C57BL
Intracellular Signaling Peptides and Proteins
Carrier Proteins
DNA-Binding Proteins
Immediate-Early Proteins
Membrane Glycoproteins
Proto-Oncogene Proteins
Transcription Factors
Repressor Proteins
DNA, Complementary
Antigens, CD
Enzyme Inhibitors
Cloning, Molecular
Signal Transduction
Cell Differentiation
Gene Expression Regulation
Amino Acid Sequence
Conserved Sequence
src Homology Domains
Sequence Homology, Amino Acid
Molecular Sequence Data
STAT3 Transcription Factor
Cytokine Receptor gp130
Suppressor of Cytokine Signaling Proteins
Protein-Tyrosine Kinases
Janus Kinase 2
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
DOI: 10.1038/43206
Appears in Collections:Aurora harvest
Medicine publications

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