title: Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation.
abstract: We report here the role of one of the less studied members of the family of suppressors of cytokine signaling (SOCS), namely SOCS-7, in cytokine signaling. We demonstrate that SOCS-7 inhibits prolactin (PRL), growth hormone (GH), or leptin (LEP) signaling mediated through STAT3 and STAT5 in a dose-dependent manner. SOCS-7 also attenuated STAT3 and STAT5 signaling induced by overexpression of JH1, the catalytic subdomain of JAK2. Since SOCS-7 interacted with phosphorylated STAT3 or STAT5, we assumed that SOCS-7 acts at the level of STAT proteins. Indeed, we showed that SOCS-7 inhibits PRL- and leptin-induced STAT5 and STAT3 phosphorylation and prevented the nuclear translocation of activated STAT3. Taken together, our results indicate that SOCS-7 is a physiological dysregulator of PRL, leptin, and probably also GH signaling and that its mode of action is a novel variation of SOCS protein inhibition of cytokine-inducible STAT-mediated signal transduction.
authors.affiliation: Neuroendocrine Immunology, and Pharmacology Department, Medical School, Free University, B-1090 Brussels, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Martens
authors.forename: Galit
authors.initials: G
authors.lastname: Uzan
authors.forename: Maxime
authors.initials: M
authors.lastname: Wery
authors.forename: Robert
authors.initials: R
authors.lastname: Hooghe
authors.forename: Elisabeth L
authors.initials: EL
authors.lastname: Hooghe-Peters
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002630:Chemotactic Factors / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; C515448:LEPR protein, human; D020738:Leptin; D008894:Milk Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011981:Receptors, Prolactin; D011993:Recombinant Fusion Proteins; C108775:SOCS7 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; C066258:platelet-derived neutrophil chemotactic peptide; D011388:Prolactin; D013006:Growth Hormone