Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus.
Components of a signaling pathway that couples the ciliary neurotrophic factor (CNTF) receptor to induction of transcription were identified. CNTF stimulated the tyrosine phosphorylation of p91, a protein implicated in interferon signaling pathways, and of two proteins that are distinct but related to p91. Tyrosine-phosphorylated p91 translocated to the nucleus, where p91 and p91-related proteins bound to a DNA sequence found in promoters of genes responsive to CNTF. This DNA sequence, when inserted upstream of a reporter gene, conferred a transcriptional response to CNTF. A pathway that transduces interferon signals may therefore have a more general function in the propagation of responses to certain neurotrophic factors.
Bonni
A
A
Program in Neuroscience, Harvard Medical School, Boston, MA 02115.
Frank
D A
DA
Schindler
C
C
Greenberg
M E
ME
D001483:Base Sequence; D001692:Biological Transport / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000737:chemistry; D019000:Phosphotyrosine; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016222:Fibroblast Growth Factor 2; D019000:Phosphotyrosine; D014443:Tyrosine; D007371:Interferon-gamma