A Dual Functional Switch in Reproductive Biology

摘要 雌激素受体的两个亚型，era和erb，在 生殖生物学。Erb既能干扰era功能，又能发挥其生物学活性。 独立于时代。目前还不清楚再培训局的独立于时代和与时代竞争的职能是如何 受监管的。我们最近开创性地发现了Erb特异性的磷酸酪氨酸开关 调节Erb在生殖器官中的功能。根据我们的初步工作，我们假设单个 磷酸酪氨酸在两种不同的Erb功能之间切换：当磷酸化的Erb处于激活状态时 在卵泡发生过程中，非磷酸化的Erb在其所处的时代更有效-- 在乳腺发育中的竞争作用。拥有一系列独特的工具，包括磷酸盐- 特异性抗体和敲打动物模型，我们处于理想的位置来检验这一新的假设 研究磷酸酪氨酸开关如何不同地调节两种不同的Erb活性。这一概念 ERb两种不同活动之间的分子切换代表了一种以前未被认识到的机制 它通过单个信令开关集成了对两个亚型特定ERb活动的控制。此外， 我们工作中开发的独特的技术工具和实验模型将极大地促进对 生殖生物学中的内分泌功能。

ABSTRACT The two subtypes of estrogen receptor, ERa and ERb, carry out non-overlapping functions in reproductive biology. ERb is capable of both interfering with ERa function and exerting its biological activity independent of ERa. It remains unclear how the ERa-independent and ERa-competing functions of ERb are regulated. We recently made the pioneering discovery of an ERb-specific phosphotyrosine switch that regulates ERb function in reproductive organs. Based on our preliminary work, we hypothesize that a single phosphotyrosine switch toggles between two different ERb functions: while phosphorylated ERb is active in its ERa-independent function in ovarian folliculogenesis, unphosphorylated ERb is more potent in its ERa- competing function in mammary gland development. With a repertoire of unique tools including a phospho- specific antibody and a knockin animal model, we are ideally positioned to test this novel hypothesis by investigating how the phosphotyrosine switch differentially regulates two distinct ERb activities. The concept of a molecular toggle between two distinct activities of ERb represents a previously unappreciated mechanism that integrates control of two subtype-specific ERb activities through a single signaling switch. In addition, the unique technical tools and experimental models developed in our work will greatly promote in-depth studies of endocrine functions in reproductive biology.