The biology and mechanism of action of suppressor of cytokine signaling 3

Babon, JJ; Nicola, NA

Author(s): Babon, JJ; Nicola, NA;
Details: Publication Year 2012-08,Volume 30,Issue #4,Page 207-219
Journal Title: GROWTH FACTORS
Publication Type: Journal Article
Abstract: Suppressors of cytokine signaling 3 (SOCS3) has been shown to be an important and non-redundant feedback inhibitor of several cytokines including leukemia inhibitory factor, IL-6, IL-11, Ciliary neurotrophic factor (CNTF), leptin, and granulocyte colony-stimulating factor (G-CSF). Loss of SOCS3 in vivo has profound effects on placental development, inflammation, fat-induced weight gain, and insulin sensitivity. SOCS3 expression is induced by Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling and it then binds to specific cytokine receptors (including gp130, G-CSF, and leptin receptors). SOCS3 then inhibits JAK/STAT signaling in two distinct ways. First, SOCS3 is able to directly inhibit the catalytic activity of JAK1, JAK2, or TYK2 while remaining bound to the cytokine receptor. Second, SOCS3 recruits elongins B/C and Cullin5 to generate an E3 ligase that ubiquitinates both JAK and cytokine receptor targeting them for proteasomal degradation. Detailed in vivo studies have revealed that SOCS3 action not only limits the duration of cytokine signaling to prevent overactivity but it is also important in maintaining the specificity of cytokine signaling.
Publisher: INFORMA HEALTHCARE
Keywords: PHYSIOLOGICAL NEGATIVE REGULATOR; HUMAN HEPATOCELLULAR-CARCINOMA; ENHANCED LEPTIN SENSITIVITY; STIMULATING FACTOR-RECEPTOR; MICE LACKING SUPPRESSOR; HIPPEL-LINDAU PROTEIN; JANUS TYROSINE KINASE; EMBRYONIC STEM-CELLS; DIET-INDUCED OBESITY; SOCS-BOX
Research Division(s): Cancer And Haematology
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757090/
Publisher's Version: https://doi.org/10.3109/08977194.2012.687375

Creation Date: 2012-08-01 12:00:00