IGF-II AND MUSCLE CELL DIFFERENTIATION

描述（改编自申请人的摘要）：通过 体液和/或自分泌/旁分泌机制，胰岛素样生长 这些因子刺激肌肉细胞的分化。 而IGF-I 和IGF-II刺激肌生成，IGF-II是主要的IGF肽 由肌肉细胞表达，因此，可能会发挥更大的作用。 在分化过程中的基本作用。 将检验IGF-II刺激肌肉细胞分化的假设 通过增加肌细胞生成素的表达和作用， 骨骼肌的主控制基因。此外，研究将测试 假设IGF-II对肌细胞生成素表达的影响是通过 通过IGF-I受体和IGF结合蛋白调节 IGF对肌细胞生成素表达和骨骼肌分化的影响。 为了检验这些假设，研究将涉及以下具体目标： (1)为了检测IGF-II对mRNA丰度、转录、 蛋白质的生物合成，以及肌细胞生成素与DNA调控元件的结合， 以及转录因子E12和Id的表达， 与肌细胞生成素二聚化的主要肽;（2）检查哪些IGF- 受体亚型介导IGF-II对表达的影响， 肌生成素和E12和Id，使用最近定义的IGF-II类似物， 对IGF-II受体在结合、交联和 mRNA丰度研究;（3）探讨IGF-1的潜在作用。 结合蛋白和IGF诱导的肌细胞生成素基因表达与IGF 对结合蛋白亲和力降低但亲和力不变的类似物 胰岛素样生长因子受体

DESCRIPTION (Adapted from the applicant's abstract): Acting through humoral and/or autocrine/paracrine mechanisms, the insulin-like growth factors stimulate the differentiation of muscle cells. Whereas both IGF-I and IGF-II stimulate myogenesis, IGF-II is the principle IGF peptide expressed by muscle cells and is, therefore, likely to play a more fundamental role in the differentiation process.Studies in this proposal will test the hypothesis that IGF-II stimulates muscle cell differentiation by increasing the expression and action of myogenin, a differentiation master control gene for skeletal muscle.In addition, studies will test the hypothesis that the effects of IGF-II on myogenin expression are mediated through the IGF-I receptor and that IGF-binding proteins modulate the effects of IGF on myogenin expression and skeletal muscle differentiation. To test these hypotheses, studies will address the following specific aims: (1) To examine the effects of IGF-II on the mRNA abundance, transcription, protein biosynthesis, and binding of myogenin onto DNA regulatory elements, and on the expression of the transcription factors, E12 and Id, the principal peptides with which myogenin dimerizes; (2) to examine which IGF- receptor subtypes mediate the effects of IGF-II on the expression of myogenin and E12 and Id, using recently defined IGF-II analogs that have selective affinity for the IGF-II receptor in binding, cross-linking, and mRNA abundance studies; and (3) to explore the potential role of IGF- binding proteins and IGF-induced myogenin gene expression with an IGF analog with reduced affinity for binding proteins but unaltered affinity for IGF receptors.