Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, Taga T, Kishimoto T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11349-53. doi: 10.1073/pnas.88.24.11349.
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.
白细胞介素6（IL-6）信号通过与IL-6和IL-6受体复合物相关联的gp130进行转导。在人gp130的细胞质区域引入截短或氨基酸取代，并将突变cDNA转染到小鼠白细胞介素3依赖性细胞中，以确定产生IL-6介导的生长信号至关重要的氨基酸残基。在gp130的277个氨基酸的细胞质区域中，靠近跨膜结构域的一个61个氨基酸的区域足以产生生长信号。在该区域中，两个短片段与其他细胞因子受体家族成员具有显著的同源性。一个片段在该家族的几乎所有成员中都是保守的，另一个片段尤其存在于粒细胞集落刺激因子受体、白细胞介素2受体β链、促红细胞生成素受体、KH97（一种粒细胞/巨噬细胞集落刺激因子受体相关分子）和白细胞介素3受体中。这两个片段中任一个发生突变的gp130分子都不能转导生长信号。具有这种突变的gp130信号转导能力的丧失与IL-6诱导的gp130酪氨酸磷酸化的消失相一致。
