HORMONE REGULATED EXPRESSION OF INSULIN RECEPTOR GENE

描述(改编自申请人的摘要)：行为 胰岛素是通过胰岛素受体(IR)介导的，胰岛素受体是 膜糖蛋白。为了传递信号，感受器 使胰岛素受体底物I的酪氨酸残基磷酸化 (IRS-I)。IRS-I在多种信号转导中与SH2结构域结合 蛋白质并触发磷酸化级联反应，从而改变 细胞功能。研究人胰岛素的调节作用 受体基因、顺式元件和反式作用因子决定 之前已经发现了转录。目标1是研究 Rb刺激hir基因表达的机制。…的行为 视网膜母细胞瘤基因产物(Rb)，细胞增殖的调节因子， 是通过聚集的SPL结合位点介导的。这是假设的 Rb可能通过隔离抑制子来诱导hir表达 蛋白。Rb调节hir基因表达的机制将 被确定和介导Rb诱导的因素 Hir基因的转录将被克隆。目标2是克隆和 描述IRNF-I和IRNF-II这两个重要的核因子 用于胰岛素受体基因转录。目标3是检查 脂肪细胞分化过程中hir基因表达的增强。这个 在脂肪细胞分化过程中，hir的表达受到高度调控。 PPARGamma2和C/EBPalpha对这一过程的可能影响将 审查并确定其作用机制。

DESCRIPTION (Adapted from the applicant's abstract): The action of insulin is mediated through the insulin receptor (IR), an integral membrane glycoprotein. To transduce a signal, the receptor phosphorylates the tyrosine residues of insulin receptor substrate I (IRS- I). IRS-I binds to the SH2 domains in various signal transduction proteins and triggers a phosphorylation cascade, thereby altering the cellular function. To study the regulation of the human insulin receptor gene, the cis-elements and trans-acting factors that determine transcription have previously been identified. Aim 1 is to study the mechanism by which Rb stimulates hIR gene expression. The action of retinoblastoma gene product (Rb), a regulator of cellular proliferation, is mediated through clustered Spl binding sites. It is hypothesized that Rb might induce hIR expression by sequestering a suppressor protein. The mechanism by which Rb regulates hIR gene expression will be determined and the factor which mediates Rb induction of transcription of the hIR gene will be cloned. Aim 2 is to clone and characterize IRNF-I and IRNF-II, two nuclear factors that are important for insulin receptor gene transcription. Aim 3 is to examine the enhancement of hIR gene expression during adipocyte differentiation. The expression of hIR is highly regulated during adipocyte differentiation. The possible effects of PPARgamma2 and C/EBPalpha on this process will be examined and the mechanisms of action determined.