SOCS3 regulates the plasticity of gp130 signaling

被引：369

作者：

Lang, R

Pauleau, AL

Parganas, E

Takahashi, Y

Mages, J

Ihle, JN

Rutschman, R

Murray, PJ

机构：

[1] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA

[2] Tech Univ Munich, Inst Med Mikrobiol Immunol & Hyg, Munich, Germany

[3] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 06期

关键词：

D O I：

10.1038/ni932

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathway. SOCS3 is upregulated by several signals in macrophages and has been implicated as a regulator of various signaling pathways. Here we show that phosphorylation of STAT3 is prolonged in mouse Socs3-deficient macrophages after stimulation with interleukin-6 (IL-6) but not IL-10, indicating that SOCS3 specifically affects signaling mediated by IL-6 and gp130. IL-6 induces a wider transcriptional response in Socs3-deficient macrophages than in wild-type cells; this response is dominated by interferon (IFN)-regulated genes owing to an excess of STAT1 phosphorylation. Thus, SOCS3 functions to control the quality of the response to IL-6 and prevents the activation of an IFN-induced program of gene expression.

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页码：546 / 550

页数：5

相关论文

共 35 条

[1] Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction [J].

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 .

JOURNAL OF LEUKOCYTE BIOLOGY, 1999, 66 (04) :588-592

[2] SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine [J].

Alexander, WS ;

Starr, R ;

Fenner, JE ;

Scott, GL ;

Handman, E ;

Sprigg, NS ;

Corbin, JE ;

Cornish, AL ;

Darwiche, R ;

Owczarek, CM ;

Kay, TWH ;

Nicola, NA ;

Hertzog, PJ ;

Metcalf, D ;

Hilton, DJ .

CELL, 1999, 98 (05) :597-608

[3] Autoregulation of pituitary corticotroph SOCS-3 expression: Characterization of the murine SOCS-3 promoter [J].

Auernhammer, CJ ;

Bousquet, C ;

Melmed, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6964-6969

[4] Involvement of suppressor of cytokine signaling-3 as a mediator of the inhibitory effects of IL-10 on lipopolysaccharide-induced macrophage activation [J].

Berlato, C ;

Cassatella, MA ;

Kinjyo, I ;

Gatto, L ;

Yoshimura, A ;

Bazzoni, F .

JOURNAL OF IMMUNOLOGY, 2002, 168 (12) :6404-6411

[5] LPS and TNFα induce SOCS3 mRNA and inhibit IL-6-induced activation of STAT3 in macrophages [J].

Bode, JG ;

Nimmesgern, A ;

Schmitz, J ;

Schaper, F ;

Schmitt, M ;

Frisch, W ;

Hussinger, D ;

Heinrich, PC ;

Graeve, L .

FEBS LETTERS, 1999, 463 (03) :365-370

[6] Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras [J].

Cacalano, NA ;

Sanden, D ;

Johnston, JA .

NATURE CELL BIOLOGY, 2001, 3 (05) :460-465

[7] Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: Evidence for an IL-10-induced pathway that is independent of STAT protein activation [J].

Cassatella, MA ;

Gasperini, S ;

Bovolenta, C ;

Calzetti, F ;

Vollebregt, M ;

Scapini, P ;

Marchi, M ;

Suzuki, R ;

Suzuki, A ;

Yoshimura, A .

BLOOD, 1999, 94 (08) :2880-2889

[8] Mutational switch of an IL-6 response to an interferon-γ-like response [J].

Costa-Pereira, AP ;

Tininini, S ;

Strobl, B ;

Alonzi, T ;

Schlaak, JF ;

Is'harc, H ;

Gesualdo, I ;

Newman, SJ ;

Kerr, IM ;

Poli, V .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (12) :8043-8047

[9] SOCS3 negatively regulates IL-6 signaling in vivo [J].

Croker, BA ;

Krebs, DL ;

Zhang, JG ;

Wormald, S ;

Willson, TA ;

Stanley, EG ;

Robb, L ;

Greenhalgh, CJ ;

Förster, I ;

Clausen, BE ;

Nicola, NA ;

Metcalf, D ;

Hilton, DJ ;

Roberts, AW ;

Alexander, WS .

NATURE IMMUNOLOGY, 2003, 4 (06) :540-545

[10] Suppressors of cytokine signaling (SOCS)-1 and SOCS-3 are induced by CpG-DNA and modulate cytokine responses in APCs [J].

Dalpke, AH ;

Opper, S ;

Zimmermann, S ;

Heeg, K .

JOURNAL OF IMMUNOLOGY, 2001, 166 (12) :7082-7089

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