Activating mechanism of CNTF and related cytokines.
Ciliary neurotrophic factor (CNTF) shares structural and functional properties with members of the hematopoietic cytokine family. It is composed of a four-helix bundle structure and shares the transmembrane signal transducing proteins, glycoprotein-130 (gp130) and leukemia inhibitory factor receptor (LIF-R). Structure-function analysis showed that the gp130-interactive proteins bind in a similar manner to that of growth hormone (site I and II). In addition, gp130-interactive proteins and granulocyte colony-stimulating factor (G-CSF) utilize another binding site (site III) at the boundary between CD loop and helix D. CNTF triggers the association of receptor components, resulting in activation of a signal transduction cascade mediated by specific intracellular protein tyrosine kinases. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways have been characterized in terms of gp130-interactive protein, and there should be other pathways and some crosstalk between them to enhance, prolong, or specify the signals.
Inoue
M
M
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Nakayama
C
C
Noguchi
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D020934:Ciliary Neurotrophic Factor; D006801:Humans; D008961:Models, Structural; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014158:Transcription, Genetic
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor