ACTIVIN STRUCTURE-FUNCTION RELATIONSHIPS

激活素是一种多能激素/生长因子，参与生殖、发育、细胞分化和存活等重要生物学功能。本项目研究该蛋白导致信号传播的分子事件。激活素与两类细胞表面突变激活素分子相互作用，研究启动信号转导的事件。我们将利用该项目获得的x射线晶体学和诱变数据来设计这些突变体。与激活素II型受体的初始相互作用将被详细分析。与这些事件的I型调节相互作用的机制将被研究。为了进一步了解相关蛋白激活素和tgf - β的特定活性，我们将生成嵌合分子，并在生物系统中针对这些因子进行测试。

Activin is a pluripotent hormone/growth factor that is involved in important biological functions including reproduction, development, and cell differentiation and survival. This Project studies the molecular events that lead to signal propagation by this protein. Activin interacts with two classes of cell surface mutant activin molecules to study the events that initiate signal transduction. We will employ X-ray crystallographic and mutagenesis data obtained by this Program to design these mutants. The initial interaction with activin type II receptors will be analyzed in detail. The mechanism of interaction with type I regulation of these events will be investigated. To further our understanding of the specific activities of the related proteins activin and TGFbeta, we will generate chimeric molecules and test these in biological systems specific for each of these factors.