MODULATION OF INSULIN RECEPTOR FUNCTION

胰岛素受体C端结构域在调节胰岛素分泌中的作用 胰岛素信号转导用多种合成的 缩氨酸 其中一种肽，称为肽HC，其结构 对应于胰岛素前受体序列的独特区域， 增强胰岛素刺激的胰岛素受体自身磷酸化 在无细胞系统和半透化细胞中， 对基础自磷酸化水平没有可检测的影响 或受体去磷酸化。 肽HC的亲脂性类似物， 硬脂酰肽HC，添加至完整中国仓鼠卵巢细胞 用编码人胰岛素的表达质粒转染 受体（CHO/HIRc）显著增强胰岛素刺激的胰岛素 受体自身磷酸化，而对配体刺激的 受体磷酸化活性的CHO细胞中过表达 IGF-1受体或EGF受体。 添加硬脂基肽HC至 CHO/HIRc细胞导致磷脂酰肌醇的显著增加， 3 '-激酶和丝裂原活化蛋白激酶活性对 胰岛素 最后，发现肽HC特异性地结合至 胰岛素受体β亚单位，但不与EGF受体。 采取 总之，我们的数据表明，十五肽相关的 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增加受体的内在 活性和信号转导。

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.