Elongin B/C Recruitment Regulates Substrate Binding by CIS

Piessevaux, Julie; Ceuninck, Leentje De; Catteeuw, Dominiek; Peelman, Frank; Tavernier, Jan

doi:10.1074/jbc.m803742200

Cited by 23 publications

(28 citation statements)

References 73 publications

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“…In mammals, SH2 domain is a target recognition motif commonly found in tyrosine kinases and involved in protein-protein interaction with phosphotyrosine residues (Machida & Mayer 2005 (Hilton 1999). Similar to SH2 domain, SOCS box also plays a role in SOCS inhibition of cytokine signaling as it can interact with elongin B/C, culin B, and Ring-box 2 to form a complex with E3 ubiquitin ligase activity (Yoshimura et al 2007) and trigger proteasomal degradation of JAK 2 by SOCS binding (Piessevaux et al 2008a). The presence of structural motifs in grass carp Socs1-3 and Cish for signal termination of JAK/STAT pathway raises the possibility that the type II SOCS in fish model may also participate in the down-regulation of cytokine signaling in a way similar to mammals.…”

Section: Discussionmentioning

confidence: 99%

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

Jiang

Jia

et al. 2016

Journal of Endocrinology

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Type II suppressor of cytokine signaling (SOCS) serve as feedback repressors for cytokines and are known to inhibit growth hormone (GH) actions. However, direct evidence for SOCS modulation of GH-induced insulin-like growth factor 1 (Igf1) expression is lacking, and the post-receptor signaling for SOCS expression at the hepatic level is still unclear. To shed light on the comparative aspects of SOCS in GH functions, grass carp was used as a model to study the role of type II SOCS in GH-induced Igf1 expression. Structural identity of type II SOCS, Socs1-3 and cytokine-inducible SH2-containing protein (Cish), was established in grass carp by 5'/3'-RACE, and their expression at both transcript and protein levels were confirmed in the liver by RT-PCR and LC/MS/MS respectively. In carp hepatocytes, GH treatment induced rapid phosphorylation of JAK 2 , STATs, MAPK, PI3K, and protein kinase B (Akt) with parallel rises in socs1-3 and cish mRNA levels, and these stimulatory effects on type II SOCS were shown to occur before the gradual loss of igf1 gene expression caused by prolonged exposure of GH. Furthermore, GH-induced type II SOCS gene expression could be negated by inhibiting JAK 2 , STATs, MEK 1/2 , P 38 MAPK , PI3K, and/or Akt respectively. In CHO cells transfected with carp GH receptor, over-expression of these newly cloned type II SOCS not only suppressed JAK 2 /STAT 5 signaling with GH treatment but also inhibited GH-induced grass carp Igf1 promoter activity. These results, taken together, suggest that type II SOCS could be induced by GH in the carp liver via JAK 2 /STATs, MAPK, and PI3K/Akt cascades and serve as feedback repressors for GH signaling and induction of igf1 gene expression.

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Section: Discussionmentioning

confidence: 99%

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

Jiang

Jia

et al. 2016

Journal of Endocrinology

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“…A major function of this family is inhibition of cytokine receptor signaling (Piessevaux et al, 2008a, 2008b). Transcriptional activation of SOCS genes usually occurs by the same cytokine signaling pathways they inhibit (Matsumoto et al, 1997; Pezet et al, 1999; Tollet-Egnell et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The SOCS box is involved in the formation of an E3 ubiquitin ligase complex with Elongin B/C, Cullin (CUL), and ring finger (RBX) proteins (Babon et al, 2008; Kamura et al, 1998, 2004; Piessevaux et al, 2008a, 2008b; Zhang et al, 1999). SOCS proteins function as part of the E3 ubiquitin ligase complex, increasing the degradation of a number of proteins.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cytokine-inducible SH2-containing protein (CIS) by ubiquitination and Elongin B/C interaction

Jensik

Arbogast

2015

Molecular and Cellular Endocrinology

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Cytokine-inducible SH2-containing protein (CIS) inhibits prolactin receptor (PRLR) signaling and acts as part of an E3 ubiquitin ligase complex through interactions with Elongin B/C proteins. This study aimed to identify CIS lysine ubiquitination sites and determine roles of ubiquitination and Elongin B/C interactions on CIS protein stability and PRLR signaling inhibition. Site-directed mutations revealed that CIS can be ubiquitinated on all six lysine residues. Elongin B/C interaction box mutation had no influence on CIS ubiquitination. CIS stability was increased by mutation of lysine residues and further enhanced by co-mutation of Elongin B/C interaction domain. CIS inhibition of STAT5B phosphorylation and casein promoter activation was dependent on CIS interactions with Elongin B/C, but not on CIS ubiquitination. These data indicate CIS protein stability is regulated through multiple mechanisms, including ubiquitination and interaction with Elongin B/C proteins, whereas CIS functional inhibition of PRLR signaling is dependent on the Elongin B/C interaction.

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“…More detailed analysis using CIS mutants revealed that CIS binding to the LR and EpoR not only depends on its SH2 domain but also on its SOCS box, with a critical role for the CIS Tyr-253 and the Elongin B/C recruitment site. Much in contrast, the SOCS box of SOCS2 does not play a role in substrate binding [11,12].…”

Section: Lrmentioning

confidence: 99%

MAPPIT: a versatile tool to study cytokine receptor signalling

Lemmens

Lievens

Tavernier

2008

Biochemical Society Transactions

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MAPPIT (mammalian protein-protein interaction trap) is a cytokine receptor-based two-hybrid method that operates in intact mammalian cells. A bait is fused C-terminally to a STAT (signal transducer and activator of transcription) recruitment-deficient receptor, whereas the prey is linked to functional STATbinding sites. When bait and prey interact a ligand-dependent complementation of the STAT recruitment deficiency occurs, leading to activation of a STAT-responsive reporter. MAPPIT is very well suited to study protein interactions involving activated cytokine receptors as the technique allows modification of the bait protein in a physiologically optimal environment. Cytokines and their receptorsCytokines are small messenger molecules that are involved in cell-cell communication and are critical to many vital processes such as embryonic development, growth, haemopoiesis and immune responses. They cannot cross the cellular membrane but make use of transmembrane receptors that capture cytokines and transmit their signal inside the cell. In this mini-review, we will mainly focus on homomeric type I cytokine receptors such as the EpoR (erythropoietin receptor), GHR (growth hormone receptor), LR (leptin receptor) and GCSFR (granulocyte colony-stimulating factor receptor). These cytokine receptors have no intrinsic kinase activity but make use of associated JAKs (Janus kinases). Upon ligand binding the JAKs are brought into close proximity enabling them to cross-phosphorylate each other. Subsequently the JAKs phosphorylate tyrosine residues in the cytoplasmic receptor tail, thereby creating docking sites for signalling molecules such as STAT (signal transducer and activator of transcription) proteins. After binding of these STATs they are phosphorylated in turn by the JAKs and translocate as dimers to the nucleus where they initiate transcription of target genes ( Figure 1A). Several mechanisms exist to modulate and terminate cytokine signalling. Among these, the SOCS (suppressor of cytokine signalling) protein Key words: cytokine receptor, mammalian protein-protein interaction trap (MAPPIT), signal transducer and activator of transcription (STAT), signal transduction, suppressor of cytokine signalling (SOCS), Toll-like receptor (TLR). Abbreviations used: βc, beta common; Epo, erythropoietin; EpoR, Epo receptor; GCSFR, granulocyte colony-stimulating factor receptor; GHR, growth hormone receptor; GM-CSF, granulocyte/macrophage colony-stimulating factor; gp130, glycoprotein 130; HEK-293T cells, human embryonic kidney cells expressing the large T-antigen of SV40 (simian virus 40); IRAK, interleukin-1-receptor-associated kinase; IRS4, insulin receptor substrate 4; JAK, Janus kinase; LR, leptin receptor; MAPPIT, mammalian protein-protein interaction trap; MyD88, myeloid differentiation primary response protein 88; Mal, MyD88 adaptor-like protein; PLCγ , phospholipase Cγ ; SH2, Src homology 2; CIS, cytokine-inducible SH2 domain-containing protein; SOCS, suppressor of cytokine signalling; STAT, signal transducer and ...

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Elongin B/C Recruitment Regulates Substrate Binding by CIS

Cited by 23 publications

References 73 publications

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

Regulation of cytokine-inducible SH2-containing protein (CIS) by ubiquitination and Elongin B/C interaction

MAPPIT: a versatile tool to study cytokine receptor signalling

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