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Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction
Author(s) -
Alexander Warren S.,
Starr Robyn,
Metcalf Donald,
Nicholson Sandra E.,
Farley Alison,
Elefanty Andrew G.,
Brysha Marta,
Kile Benjamin T.,
Richardson Rachel,
Baca Manuel,
Zhang JianGuo,
Willson Tracy A.,
Viney Elizabeth M.,
Sprigg Naomi S.,
Rakar Steven,
Corbin Jason,
Mifsud Sandra,
DiRago Ladina,
Cary Dale,
Nicola Nicos A.,
Hilton Douglas J.
Publication year - 1999
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.66.4.588
Subject(s) - biology , signal transduction , socs3 , haematopoiesis , suppressor of cytokine signalling , cytokine , stat , janus kinase , microbiology and biotechnology , sh2 domain , knockout mouse , stat3 , immunology , receptor , genetics , tyrosine kinase , stem cell
SOCS‐1 was originally identified as an inhibitor of interleukin‐6 signal transduction and is a member of a family of proteins (SOCS‐1 to SOCS‐7 and CIS) that contain an SH2 domain and a conserved carboxyl‐terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino‐terminal and SH2 domains are essential for SOCS‐1 and SOCS‐3 to inhibit cytokine signaling. Inhibition of cytokine‐dependent activation of STAT3 occurred in cells expressing either SOCS‐1 or SOCS‐3, but unlike SOCS‐1, SOCS‐3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS‐1 and SOCS‐3 action when over‐expressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS‐1 −/− mice were born but failed to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS‐1 −/− mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS‐1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects. J. Leukoc. Biol. 66: 588–592; 1999.