PMID- 9202125
OWN - NLM
STAT- MEDLINE
DCOM- 19970717
LR  - 20240109
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 387
IP  - 6636
DP  - 1997 Jun 26
TI  - A family of cytokine-inducible inhibitors of signalling.
PG  - 917-21
AB  - 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.
FAU - Starr, R
AU  - Starr R
AD  - The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, 
      Australia.
FAU - Willson, T A
AU  - Willson TA
FAU - Viney, E M
AU  - Viney EM
FAU - Murray, L J
AU  - Murray LJ
FAU - Rayner, J R
AU  - Rayner JR
FAU - Jenkins, B J
AU  - Jenkins BJ
FAU - Gonda, T J
AU  - Gonda TJ
FAU - Alexander, W S
AU  - Alexander WS
FAU - Metcalf, D
AU  - Metcalf D
FAU - Nicola, N A
AU  - Nicola NA
FAU - Hilton, D J
AU  - Hilton DJ
LA  - eng
SI  - GENBANK/U88325
SI  - GENBANK/U88326
SI  - GENBANK/U88327
SI  - GENBANK/U88328
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, CD)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (IL6ST protein, human)
RN  - 0 (Il6st protein, mouse)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOCS1 protein, human)
RN  - 0 (SOCS2 protein, human)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Socs1 protein, mouse)
RN  - 0 (Socs2 protein, mouse)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (cytokine inducible SH2-containing protein)
RN  - 133483-10-0 (Cytokine Receptor gp130)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, CD/physiology
MH  - *Carrier Proteins
MH  - Cell Differentiation/physiology
MH  - Cloning, Molecular
MH  - Conserved Sequence
MH  - Cytokine Receptor gp130
MH  - Cytokines/antagonists & inhibitors/physiology
MH  - DNA, Complementary
MH  - DNA-Binding Proteins/physiology
MH  - Enzyme Inhibitors
MH  - Feedback
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immediate-Early Proteins/chemistry/genetics
MH  - Interleukin-6/*antagonists & inhibitors/physiology
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Janus Kinase 2
MH  - Macrophages/cytology/*physiology
MH  - Membrane Glycoproteins/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/physiology
MH  - Proteins/chemistry/genetics/*physiology
MH  - *Proto-Oncogene Proteins
MH  - *Repressor Proteins
MH  - STAT3 Transcription Factor
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins
MH  - Trans-Activators/physiology
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
MH  - src Homology Domains
EDAT- 1997/06/26 00:00
MHDA- 2001/03/23 10:01
CRDT- 1997/06/26 00:00
PHST- 1997/06/26 00:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1997/06/26 00:00 [entrez]
AID - 10.1038/43206 [doi]
PST - ppublish
SO  - Nature. 1997 Jun 26;387(6636):917-21. doi: 10.1038/43206.