HORMONE REGULATED EXPRESSION OF INSULIN RECEPTOR GENE

描述（改编自申请人摘要）： 胰岛素是通过胰岛素受体（IR）介导的， 膜糖蛋白为了抑制信号，受体 磷酸化胰岛素受体底物I的酪氨酸残基 (IRS-（一）。IRS-I在各种信号转导中与SH 2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 转录以前已经确定。目的1是研究 Rb刺激hIR基因表达的机制。的作用 视网膜母细胞瘤基因产物（Rb），一种细胞增殖的调节剂， 通过成簇的Spl结合位点介导。据推测 Rb可能通过抑制hIR基因表达， 蛋白Rb调控hIR基因表达的机制将 确定和介导Rb诱导的因子， 将克隆hIR基因的转录。目标2是克隆和 描述IRNF-I和IRNF-II，两个重要的核因子， 胰岛素受体基因的转录。目标3是检查 脂肪细胞分化过程中hIR基因表达的增强。的 hIR的表达在脂肪细胞分化过程中受到高度调节。 PPARgamma 2和C/EBPalpha对这一过程的可能影响将 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.