Insulin Receptor Substrate 4 Couples the Leptin Receptor to Multiple Signaling Pathways

Wauman, Joris; Smet, A. De; Catteeuw, Dominiek; Belsham, Denise D.; Tavernier, Jan

doi:10.1210/me.2007-0414

Cited by 55 publications

(52 citation statements)

References 66 publications

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“…(i) MMP14 modulates glycolysis and is regulated by leptin, the famous obese gene product (38). (ii) Insulin receptor substrate 4 (IRS4), in addition to its known function in insulin-Akt-mTOR signaling, directly binds to and modulates signaling through the leptin receptor (39). (iii) PDPK-1, CHRNB2, GAS6, and the brain-derived neurotrophic factor receptor TrkB have been implicated in body weight control (40 -43).…”

Section: Functions Of Midas-containing Mrnas Concentrate On Developmementioning

confidence: 99%

Protein Phosphatase 2A (PP2A)-specific Ubiquitin Ligase MID1 Is a Sequence-dependent Regulator of Translation Efficiency Controlling 3-Phosphoinositide-dependent Protein Kinase-1 (PDPK-1)

Aranda-Orgillés

Rutschow

Zeller

et al. 2011

Journal of Biological Chemistry

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Background: MID1, a regulator of PP2A, forms part of a messenger ribonucleoprotein complex. Results: MID1 complex binds a purine-rich sequence motif in mRNAs and regulates their translation. Conclusion:The translation of mRNAs bound by the MID1 complex is impaired in patients with Opitz syndrome. Significance: This study shows how coordinated translation of specific mRNAs can be regulated and provides new strategies for therapies and biotechnology.

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Section: Functions Of Midas-containing Mrnas Concentrate On Developmementioning

confidence: 99%

Protein Phosphatase 2A (PP2A)-specific Ubiquitin Ligase MID1 Is a Sequence-dependent Regulator of Translation Efficiency Controlling 3-Phosphoinositide-dependent Protein Kinase-1 (PDPK-1)

Aranda-Orgillés

Rutschow

Zeller

et al. 2011

Journal of Biological Chemistry

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“…More recently, MAPPIT experiments in both HEK-293T and in the physiologically highly relevant N38 hypothalamic cell line revealed that IRS4 (insulin receptor substrate 4) interacts with the Tyr-1077 motif. Using IRS4 as bait, we confirmed the interaction with the p85 subunit of PI3K (phosphoinositide 3-kinase), SOCS6 and SOCS7 and documented interactions with PLCγ and SOCS2 [13].…”

Section: Lrmentioning

confidence: 56%

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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“…Several members of the insulin receptor substrate (IRS) family allow leptin induced PI3K activation and phosphatidylinositol 3,4,5-triphosphate (PIP3) production [9,28,63,128]. This in turn leads to the activation of 3-phosphoinositide-dependent protein kinase 1 (PDK1), Akt and cyclic nucleotide phosphodiesterase 3B (PDE3B), a cAMPdegrading enzyme [141].…”

Section: Lr Signalingmentioning

confidence: 99%

“…Follow-up in vitro experiments and studies in db/db mice showed that these effects do not require interaction with the LR long form. Nonetheless, LEP- (116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129)(130) was proven to promote luteinizing hormone (LH) and prolactin (PRL) secretion in fasted animal rats [49].…”

Section: Leptin Peptide Modulatorsmentioning

confidence: 99%