MODULATION OF INSULIN RECEPTOR FUNCTION

胰岛素受体C端结构域在调节血管紧张素转换酶中的作用 胰岛素信号转导被探索与各种合成的 多肽。一种多肽，称为多肽HC，其结构 对应于胰岛素前受体序列的一个独特区域， 增强胰岛素刺激的胰岛素受体的自磷酸化 在无细胞体系和半渗透细胞中 对基础自动磷酸化水平没有可检测到的影响 或受体去磷酸化。多肽HC的亲脂性类似物， 硬脂酰多肽HC加入完整的中国仓鼠卵巢细胞 用编码人胰岛素的表达载体转染 受体(CHO/HIRc)显著增强胰岛素刺激的胰岛素 受体自动磷酸化对配体刺激无影响 CHO细胞的受体磷酸化活性过表达 IGF-1受体或EGF受体。硬脂酰基多肽HC的加成 CHO/HIRc细胞磷脂酰肌醇显著增加 3‘-激酶和丝裂原活化蛋白激酶活性对 胰岛素。最后，我们发现，多肽HC可以特异性地与 胰岛素受体β亚基，但不与EGF受体结合。已被占用 总而言之，我们的数据表明，与细胞周期相关的十五肽 胰岛素受体的C末端与受体β亚基结合， 这种相互作用可能有助于受体的增加~S内在 活动和信号转导。

The role of the insulin receptor C-terminal domain in the regulation of insulin signal transduction was explored with a variety of synthetic peptides. One of the peptides, termed peptide HC whose structure corresponds to an unique region of the insulin proreceptor sequence, enhanced insulin-stimulated autophosphorylation of the insulin receptor in cell-free systems and in semi-permeabilized cells at concentrations where there were no detectable effect on basal autophosphorylation levels or on receptor dephosphorylation. A lipophilic analogue of peptide HC, stearyl-peptide HC, added to intact Chinese hamster ovary cells transfected with an expression plasmid encoding the human insulin receptor (CHO/HIRc) enhanced significantly insulin-stimulated insulin receptor autophosphorylation while having no effect on ligand-stimulated receptor phosphorylation activity in CHO cells overexpressing either the IGF-1 receptor or the EGF receptor. Addition of stearyl-peptide HC to CHO/HIRc cells resulted in a significant increase in phosphatidylinositol 3'-kinase and mitogen-activated protein kinase activities in response to insulin. Finally, it was found that peptide HC specifically bind to the insulin receptor BETA-subunit but not with the EGF receptor. Taken together our data demonstrate that a pentadecapeptide related to the C-terminus of the insulin receptor bind to the receptor beta-subunit and that this interaction may contribute to the increased receptor~s intrinsic activity and signal transduction.