Analysis of leptin signalling in hematopoietic cells using an adapted MAPPIT strategy

Montoye, Tony; Piessevaux, Julie; Lavens, Delphine; Wauman, Joris; Catteeuw, Dominiek; Vandekerckhove, Joël; Lemmens, Irma; Tavernier, Jan

doi:10.1016/j.febslet.2006.04.094

Cited by 22 publications

(15 citation statements)

References 28 publications

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“…9 Phosphorylation of Tyr985 also promotes recruitment of SHP2 for activation of extracellular signalYregulated kinase as well as attenuation of RasGTPase-p62Dok, leading to stimulation of Ras activity and cell proliferation. 23 Tyr1077 phosphorylation of Ob-Rb induces activation of STAT5, resulting in peroxisome proliferatorY activated receptor F overexpression 23 Previously, Pallares et al 24 that found NF-JB family may be important in endometrial carcinogenesis, by controlling apoptosis and cell proliferation after they detected NF-JB family and IJB families expression in human EC. In our experiments, leptin induced NIK/IKK phosphorylation and subsequent NF-JB activation, leading to inhibition of EC cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB–inducing Kinase/IκB Kinase Pathway

Zhou

Chai

et al. 2015

International Journal of Gynecological Cancer

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Section: Discussionmentioning

confidence: 99%

Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB–inducing Kinase/IκB Kinase Pathway

Zhou

Chai

et al. 2015

International Journal of Gynecological Cancer

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“…SOCS2 can impair the inhibitory effect of SOCS1 or SOCS3 on leptin-induced signalling (69), and it can interfere with the association of CIS to the OB-R membrane proximal tyrosine (70). Also SOCS6 and SOCS7 can interact with the OB-R. SOCS7 may be implicated in OB-R signalling termination (71), i.e. by inhibiting STAT3 activation and/or by interacting with activated STAT3 to prevent translocation to the nucleus (72).…”

Section: Suppressors Of Cytokine Signalling (Socs)mentioning

confidence: 99%

Leptin Signaling: A Key Pathway in Immune Responses

Procaccini

Lourenço

Matarese

et al. 2009

CST

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Leptin is a hormone whose central role is to regulate endocrine functions and to control energy expenditure. After the discovery that leptin can also have pro-inflammatory effects, several studies have tried to address - at the molecular level - the pathways involved in leptin-induced modulation of the immune functions in normal and pathologic conditions. The signaling events influenced by leptin after its binding to the leptin receptor have been under scrutiny in the past few years, and considerable experimental work has elucidated the consequences of leptin effects on immune cells. This review examines the biochemistry, function and regulation of leptin signaling in view of possible intervention on this molecule for a better management and therapy of immune-mediated diseases.

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“…Using the βc setup ( Figure 1F), we confirmed the binding of CIS, SOCS2 and STAT5a to the Tyr-1077 motif in the murine Ba/F3 pro-B cell line and revealed that, in addition, PLCγ , SOCS6 and SOCS7 also interact with the Tyr-1077 motif [8]. 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.…”

Section: Lrmentioning

confidence: 64%

“…To be able to use MAPPIT in haemopoietic cells that have no or very low STAT3 levels, βc (beta common) MAPPIT was created, which employs STAT5 as a signal transducer. To accomplice this, the prey was fused to a portion of the βc chain containing STAT5 recruitment sites ( Figure 1F) [8].…”

Section: Mappit (Mammalian Protein-protein Interaction Trap)mentioning

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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Analysis of leptin signalling in hematopoietic cells using an adapted MAPPIT strategy

Cited by 22 publications

References 28 publications

Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB–inducing Kinase/IκB Kinase Pathway

Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB–inducing Kinase/IκB Kinase Pathway

Leptin Signaling: A Key Pathway in Immune Responses

MAPPIT: a versatile tool to study cytokine receptor signalling

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