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

Alexander, WS; 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

Author(s): Alexander, WS; 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;
Details: Publication Year 1999-10,Volume 66,Issue #4,Page 588-592
Journal Title: JOURNAL OF LEUKOCYTE BIOLOGY
Publication Type: Journal Article
Abstract: 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.
Publisher: FEDERATION AMER SOC EXP BIOL
Keywords: INTERFERON-GAMMA; INDUCIBLE GENE; PROTEIN; DIFFERENTIATION; DEFICIENCIES; PROTEASOMES; INVOLVEMENT; EXPRESSION; ACTIVATION; INHIBITOR
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Creation Date: 1999-10-01 12:00:00