Fc receptor signal initiation mechanisms at lipid rafts

抗原受体，包括T细胞和B细胞受体以及免疫球蛋白Fc部分的受体（igg的Fc受体），在免疫调节的初始阶段起着核心作用。假设受体接合被Src家族激酶（SFKs）感知并转化为细胞内部事件。为了阐明SFK的特异性，我们引入了新的策略，并确定了它们在Fc、c-Kit和整合素受体中的需求和特异性。值得注意的是，负责Fc受体信号传导的sfk都被棕榈酸修饰，并且它们驻留在称为“脂筏”的膜结构域中。我们还表明，特殊的脂筏聚结是SFK激活的上游事件。我们可以假设筏状聚结为sfk相互反激活提供了一个场。我们正在寻找负责Fc受体介导的脂质筏组装的分子。接下来，我们克隆了两个与SFK相互作用的新分子，Lyn。一个具有RING结构域，另一个是一个巨大的接头蛋白，具有假定的Grb2和PI3K结合位点和GAP结构域。第三，我们正在研究IgG负调控Fc受体（Fcγ riib）多态性形式的功能差异，其中一个（罕见等位基因）与系统性红斑狼疮遗传相关。

Antigen receptors, consists of T and B cell receptors and those for Fc portion of Immunoglobulines (Fc receptors for Igs) play central roles in the initial step of immune regulation. It was assumed that receptor engagement is sensed and converted by Src family kinases (SFKs) to cell-inner events. To elucidate the SFK specificity, we introduced novel strategies and established their requirement and specificity in Fc, and c-Kit and Integrin receptors. Notably, SFKs responsible for Fc receptor signaling are all modified with palmitic acid, and they reside in a membrane domain referred to as 'lipid rafts'. We have also shown that special lipid raft-coalescence is an upstream event to SFK activation. It could be assumed that raft-coalescence provides a field for SFKs transactivate on another. We are searching for the molecule(s) responsible for Fc receptor-mediated lipid raft assembly. Next we have cloned two novel molecules interacting with a SFK, Lyn. One possess RING domain and another is a huge adaptor protein possessing putative Grb2 and PI3K binding sites and GAP domain. Third, we are investigating functional differences in polymorphic forms of negatige regulatory Fc receptor for IgG (FcγRIIb), one of which (rare allele) is genetically linked to systemic lupus erythematodes.