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Emerging roles of suppressor of cytokine signaling 3 in human cancers.
Biomed Pharmacother
December 2021
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China; Henan International Joint Laboratory of Glioma Metabolism and Microenvironment Research, Zhengzhou, Henan, China. Electronic address:
As a member of the suppressor of cytokine signaling (SOCS) family, SOCS3 is a cytokine-inducible protein that inhibits cytokine signaling in a variety of signaling pathways. Increasing evidence shows that SOCS3 regulates tumor development through multiple pathological and physiological processes. It is worth mentioning that SOCS3 negatively regulates JAK/STAT signaling by binding to JAK/cytokine receptors or phosphorylation docking sites on STAT receptors, thus preventing tumor cell proliferation and inhibiting tumor cell invasion and metastasis.
View Article and Find Full Text PDFCrystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.
J Mol Biol
November 2016
Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address:
The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1.
View Article and Find Full Text PDFJAK-cytokine receptor recognition, unboxed.
Nat Struct Mol Biol
May 2014
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA, and the Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition.
Nat Struct Mol Biol
April 2013
Department of Structural Biology, Walter and Eliza Hall Institute, Parkville, Australia.
The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of Janus kinases (JAKs) that initiate signaling within the cell. We determined the crystal structure of a ternary complex between mouse SOCS3, JAK2 (kinase domain) and a fragment of the interleukin-6 receptor β-chain.
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