SOCS: physiological suppressors of cytokine signaling
- Author(s)
- Krebs, DL; Hilton, DJ;
- Details
- Publication Year 2000-08-01,Volume 113,Issue #16,Page 2813-2819
- Journal Title
- JOURNAL OF CELL SCIENCE
- Publication Type
- Journal Article
- Abstract
- Cytokines regulate cellular behavior by interacting with receptors on the plasma membrane of target cells and activating intracellular signal transduction cascades such as the JAK-STAT pathway. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling. The SOCS family consists of eight proteins: SOCS1-SOCS7 and CIS, each of which contains a central Src-homology 2 (SH2) domain and a C-terminal SOCS box. The expression of CIS, SOCS1, SOCS2 and SOCS3 is induced in response to stimulation by a wide variety of cytokines, and overexpression of these proteins in cell lines results in inhibition of cytokine signaling. Thus, SOCS proteins appear to form part of a classical negative feedback loop. The analysis of mice lacking SOCS1 has revealed that it is critical in the negative regulation of IFN gamma signaling and in the differentiation of T cells. Additionally, the analysis of mouse embryos lacking SOCS3 suggests that SOCS3 negatively regulates fetal liver erythropoiesis, probably through its ability to modulate erythropoietin (Epo) signaling. Thus, the use of gene targeting has confirmed that SOCS proteins regulate cytokine signaling in a physiological setting.
- Publisher
- COMPANY OF BIOLOGISTS LTD
- Keywords
- INDUCED STAT INHIBITOR; ERYTHROPOIETIN RECEPTOR; LEPTIN RESISTANCE; TYROSINE RESIDUES; GENE-EXPRESSION; SH2 DOMAIN; BOX MOTIF; PROTEIN; ACTIVATION; TRANSDUCTION
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- Refer to copyright notice on published article.
Creation Date: 2000-08-01 12:00:00