Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor.
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.
Derouet
Damien
D
Institut National de la Santé et de la Recherche Médicale U564, Centre Hospitalier Universitaire d'Angers, 4 Rue Larrey, 49033 Angers, France.
Rousseau
François
F
Alfonsi
Fabienne
F
Froger
Josy
J
Hermann
Jacques
J
Barbier
Fabien
F
Perret
David
D
Diveu
Caroline
C
Guillet
Catherine
C
Preisser
Laurence
L
Dumont
Agnès
A
Barbado
Maud
M
Morel
Alain
A
deLapeyrière
Odile
O
Gascan
Hugues
H
Chevalier
Sylvie
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology*
D015850:Interleukin-6; D020801:Receptor, Ciliary Neurotrophic Factor; C486482:neuropoietin, mouse; D004247:DNA