Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family.
Interleukin 6 (IL-6) signal is transduced through gp130 that associates with a complex of IL-6 and IL-6 receptor. Truncations or amino acid substitutions offe introduced in the cytoplasmic region of human gp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL-6-mediated growth signal. In the 277-amino acid cytoplasmic region of gp130, a 61-amino acid region proximal to the transmembrane domain was sufficient for generating the growth signal. In this region, two short segments were significantly homologous with other cytokine-receptor family members. One segment is conserved in almost all members of the family, and the other is found especially in granulocyte colony-stimulating factor receptor, interleukin 2 receptor beta chain, erythropoietin receptor, KH97 (a granulocyte/macrophage colony-stimulating factor receptor-associated molecule), and interleukin 3 receptor. gp130 molecules with mutations in either of these two segments could not transduce growth signal. Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation of gp130.
Murakami
M
M
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Narazaki
M
M
Hibi
M
M
Yawata
H
H
Yasukawa
K
K
Hamaguchi
M
M
Taga
T
T
Kishimoto
T
T
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D005075:Biological Evolution; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000276:immunology*; D003593:Cytoplasm / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007700:Kinetics; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000493:pharmacokinetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D019947:Receptors, Interleukin-6; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D016207:Cytokines; C494199:IL6ST protein, human; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130