Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction

被引:102
作者
Alexander, WS [1 ]
Starr, R
Metcalf, D
Nicholson, SE
Farley, A
Elefanty, AG
Brysha, M
Kile, BT
Richardson, R
Baca, M
Zhang, JG
Willson, TA
Viney, EM
Sprigg, NS
Rakar, S
Corbin, J
Mifsud, S
DiRago, L
Cary, D
Nicola, NA
Hilton, DJ
机构
[1] PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[2] PO Royal Melbourne Hosp, Cooperat Res Ctr Cellular Growth Factors, Melbourne, Vic 3050, Australia
关键词
JAK; STAT;
D O I
10.1002/jlb.66.4.588
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
SOCS-1 tvas 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 overexpressed, 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.
引用
收藏
页码:588 / 592
页数:5
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