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The SOCS proteins: a new family of negative regulators of signal transduction
Author(s) -
Nicholson Sandra E.,
Hilton Douglas J.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.6.665
Subject(s) - biology , signal transduction , microbiology and biotechnology , transduction (biophysics) , genetics , biochemistry
The negative regulation of cytokine signaling, with the exception of the tyrosine phosphatases, is not widely understood. We recently identified a new family of negative regulators by retroviral expression of hematopoietic cDNA library in the monocytic leukemic cell line, M1. This was coupled with selection for cells that were no longer able to differentiate in response to interleukin‐6. From this screen, SOCS‐1 was cloned and was shown to arrest cytokine signaling by binding to and inhibiting the intrinsic enzymatic activity of the JAK family of protein tyrosine kinases. SOCS‐1 expression is induced in response to a range of cytokines and as such is thought to form part of a classic negative feedback loop. The SOCS family of proteins is linked by the presence of a conserved carboxy‐terminal domain termed the SOCS box and now encompasses five distinct protein groups on the basis of the structural elements found amino‐terminal to the SOCS box: (1) those that contain SH2 domains, (2) those that contain WD‐40 repeats, (3) ankyrin repeats, (4) SPRY domains, and (5) GTPase domains. As yet the function of the SOCS box remains unknown, but given the level of conservation within such diverse proteins, it is likely to have a broadly similar role in each. J. Leukoc. Biol . 63: 665–668; 1998.