Open AccessNeuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor
Author(s) -
Damien Derouet,
François Rousseau,
Fabienne Alfonsi,
Josy Froger,
Jacques Hermann,
Fabien Barbier,
David Perret,
Caroline Diveu,
Catherine Guillet,
Laurence Preisser,
Agnès Dumont,
Maud Barbado,
Alain Morel,
Odile deLapeyrière,
Hugues Gascan,
Sylvie Chevalier
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0306178101
Subject(s) - ciliary neurotrophic factor , glycoprotein 130 , microbiology and biotechnology , leukemia inhibitory factor , biology , leukemia inhibitory factor receptor , cytokine , suppressor of cytokine signaling 1 , signal transduction , socs2 , neurotrophic factors , cytokine receptor , receptor , medicine , immunology , interleukin 6 , stat3 , biochemistry , suppressor , gene
A structural profile-based computational screen was used to identify neuropoietin (NP), a new cytokine. The np gene is localized in tandem with the cardiotrophin-1 gene on mouse chromosome 7. NP shares structural and functional features with ciliary neurotrophic factor (CNTF), cardiotrophin-1, and cardiotrophin-like cytokine. It acts through a membrane receptor complex comprising CNTF receptor-alpha component (CNTFRalpha), gp130, and leukemia inhibitory factor receptor to activate signal transducer and activator of transcription 3 signaling pathway. NP is highly expressed in embryonic neuroepithelia. Strikingly, CNTFRalpha, but not its alternate ligands, CNTF and cardiotrophin-like cytokine, is expressed at the same developmental stages. NP is also observed in retina and to a lesser extent in skeletal muscle. Moreover, NP could sustain the in vitro survival of embryonic motor neurons and could increase the proliferation of neural precursors when associated to epidermal growth factor and fibroblast growth factor 2. Thus, NP is a new ligand for CNTFRalpha, with important implications for murine nervous system development.