信号转导
伤亡人数
受体
细胞生物学
生物
白细胞介素-1受体
信号转导衔接蛋白
白细胞介素
免疫学
遗传学
细胞因子
作者
Adriana Heguy,Cosima T. Baldari,G Macchia,John L. Telford,Marialuisa Melli
标识
DOI:10.1016/s0021-9258(18)45924-8
摘要
The cytoplasmic domain of the human T cell-type interleukin-1 receptor (hIL-1R) is not involved in the binding, internalization, or nuclear localization of interleukin-1 (ILl), but is essential for signal transduction.We have previously localized a 60-amino acid region (residues 477-627) critical for IL-1-mediated activation of the interleukin-2 promoter in T cells.This region displays a striking degree of amino acid conservation in human, murine, and chicken IL-1Rs.Here we report the results of a site-directed mutational analysis of the cytoplasmic domain of the hIL-1R.We have introduced single-amino acid substitutions at positions conserved in all three receptors and at nonconserved positions and identified key amino acids for IL-1R function in signal transduction.Three basic (Arg431, LysSls, and Arg'l') and 3 aromatic (PheS13, TrpSl4, and Tyr'l') amino acids that are conserved in human, murine, and chicken IL-1Rscould not be replaced without abolishing IL-la-mediated signal transduction.A substitution at another conserved position (ProS2l) reduces significantly the ability of the IL-1R to transmit the IL-1 signal.Nonconserved residues could be replaced without affecting signal transduction.The cytoplasmic domain of the IL-1R is related to that of the Drosophila Toll protein, with a 26% identity and a 43% similarity in amino acid sequence.The amino acids shown to be essential for IL-1R function are conserved in the Toll protein.Our experimental data indicate that the amino acid sequence similarity between the IL-1R and the Drosophila toll protein reflects a functional homology between the two proteins.The interactions of signalling molecules with cell-surface receptors are a main avenue through which information from the environment is channeled to different cell types.Such interactions are crucial in triggering cell differentiation and proliferation.The molecular characterization of a number of growth factor and hormone receptors has allowed the identification of the initial steps of signal transduction.In some cases, such as the epidermal growth factor receptor or the insulin receptor, ligand binding turns on a protein kinase activity intrinsic to the receptor (for review, see Ullrich and Schlessinger (1990)).For some other receptors, including the nerve growth factor (Johnson et al., 1986), tumor necrosis
科研通智能强力驱动
Strongly Powered by AbleSci AI