Fc receptor signal initiation mechanisms at lipid rafts

由T和B细胞受体组成的抗原受体和免疫球蛋白Fc部分的抗原受体（Ig的Fc受体）在免疫调节的初始步骤中起中心作用。据推测，受体的参与是由Src家族激酶（SFK）感知并转化为细胞内事件。为了阐明SFK的特异性，我们引入了新的策略，并建立了它们在Fc、c-Kit和整联蛋白受体中的要求和特异性。值得注意的是，负责Fc受体信号传导的SFK都被棕榈酸修饰，并且它们位于被称为“脂质筏”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。可以假设筏状聚结为SFK在另一个上的反式激活提供了场所。我们正在寻找负责Fc受体介导的脂筏组装的分子。接下来，我们克隆了两个新的分子与SFK，林恩相互作用。一个具有RING结构域，另一个是具有推定的Grb 2和PI 3 K结合位点和GAP结构域的巨大衔接蛋白。第三，我们正在研究IgG的负调节性Fc受体（FcγRIIb）的多态性形式的功能差异，其中一种（罕见等位基因）与系统性狼疮相关。

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.