Cytokine‐inducible SH2 protein‐3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N‐terminal kinase inhibitory region as well as SH2 domain

@article{Sasaki1999CytokineinducibleSP,
  title={Cytokine‐inducible SH2 protein‐3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N‐terminal kinase inhibitory region as well as SH2 domain},
  author={Atsuo T. Sasaki and Hideo Yasukawa and Asuka Suzuki and Shintaro Kamizono and Takanori Syoda and Ichiko Kinjyo and Mika Sasaki and James A Johnston and Akihiko Yoshimura},
  journal={Genes to Cells},
  year={1999},
  volume={4}
}
The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes involved in cell growth, differentiation and transformation through their association with cytokine receptors. We have recently identified the JAK‐binding protein, JAB that inhibits various cytokine‐dependent JAK signalling pathways. JAB inhibits JAK2 tyrosine kinase activity by binding to the kinase domain (JH1 domain) through the N‐terminal kinase inhibitory region (KIR) and the SH2 domain. The SH2 domain of JAB… 
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References

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The JAK‐binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop
TLDR
It is demonstrated that JAB specifically binds to the tyrosine residue (Y1007) in the activation loop of JAK2, whose phosphorylation is required for activation of kinase activity.
A new protein containing an SH2 domain that inhibits JAK kinases
TLDR
A new SH2-domain-containing protein is isolated, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain, and JAB and CIS appear to function as negative regulators in the JAK signalling pathway.
The CIS/JAB family: novel negative regulators of JAK signaling pathways
TLDR
CIS3 and JAB directly binds to the kinase domain of JAKs, thereby inhibiting tyrosine kinase activity, suggesting that elevated expression of JAB is involved in interferon-resistance.
A novel cytokine‐inducible gene CIS encodes an SH2‐containing protein that binds to tyrosine‐phosphorylated interleukin 3 and erythropoietin receptors.
TLDR
A novel gene, CIS (cytokine inducible SH2‐containing protein), which is induced in hematopoietic cells by a subset of cytokines but not by stem cell factor, granulocyte colony‐stimulating factor and IL6 is isolated.
A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons.
TLDR
The results suggest that JAB inhibits IFN signaling by blocking JAK activity, and found that IFN-resistant clones derived from LoVo cells and Daudi cells expressed high levels of JAB without stimulation, which could be, at least in part, a mechanism of IFN resistance.
Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop
TLDR
The results demonstrate the critical role of phosphorylation of Y1007 in Jak2 regulation and function and demonstrate that among a variety of sites, Y1007 and Y1008 are sites of trans- or autophosphorylation in vivo and in in vitro kinase reactions.
A family of cytokine-inducible inhibitors of signalling
TLDR
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.
Cloning and characterization of novel CIS family genes.
TLDR
Three additional CIS family genes (CIS2, CIS3, and CIS4) are cloned on the basis of an expression sequence tag (EST) database search and could play a role in the negative regulation of cytokine signaling by interacting with specific targets.
CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells
TLDR
It is suggested that CIS3 is a weaker inhibitor than JAB against JAK signaling, and JAB and CIS3 possess different regulatory roles in cytokine signaling.
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