SOCS3 and its role in associated diseases

Hum Immunol. 2015 Oct;76(10):775-80. doi: 10.1016/j.humimm.2015.09.037. Epub 2015 Sep 30.

Abstract

Cell-cell communication depends on cytokine and growth factor network. Bound to their receptors on the surface of target cell, these glycoproteins initiate a range of intracellular events. Subsequent dissipation of receptor signaling is essential to ensure the response of the cell does not become pathogenic. The Suppressors of cytokine signaling (SOCS) proteins are a family of proteins induced to attenuate cytokine signal transduction in response to signals from a diverse range of cytokines and growth factors. Current evidence indicates that intracellular JAK-STAT (Janus kinase-signal transducer and activator of transcription) signaling not only governs cytokine-induced immunological responses but also rapidly initiates SOCS expression and its biological functions. This review focuses on current understanding of SOCS3, a member of SOCS family. SOCS3 binds to JAK, certain cytokine receptors in intracellular domain, and some signaling molecules, which results in suppressing further signaling events in the cell. Studies using conditional knockout mice have shown that SOCS3 protein is the key physiological regulator and plays an important pathological role in immune homeostasis. Dysregulation of SOCS3 functions can cause a variety of diseases, including allergy, autoimmune diseases, inflammation and cancer.

Keywords: Cytokine; Immune homeostasis; JAK–STAT signaling; SOCS3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Asthma / genetics*
  • Asthma / immunology
  • Asthma / pathology
  • Cell Communication / immunology
  • Gene Expression Regulation
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Janus Kinases / genetics
  • Janus Kinases / immunology
  • Mice
  • Mice, Knockout
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Protein Binding
  • Receptors, Cytokine
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / immunology
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Suppressor of Cytokine Signaling Proteins / immunology

Substances

  • Receptors, Cytokine
  • SOCS3 protein, human
  • STAT Transcription Factors
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Janus Kinases