Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation.
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.
Martens
Nele
N
Neuroendocrine Immunology, and Pharmacology Department, Medical School, Free University, B-1090 Brussels, Belgium.
Uzan
Galit
G
Wery
Maxime
M
Hooghe
Robert
R
Hooghe-Peters
Elisabeth L
EL
Gertler
Arieh
A
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
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