Function of the haematopoietic GTPase RhoH in mast cell signalling

造血 GTP 酶 RhoH 在肥大细胞信号传导中的功能

• 批准号: 5443995
• 负责人: Professorin Dr. Katharina Hieke-Kubatzky
• 金额: --
• 依托单位: Abteilung Medizinische Mikrobiologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5443995?language=en
• 关键词: Function; haematopoietic; GTPase; RhoH; mast

RhoH is a haematopoiesis specific, GTPase-deficient member of the family of Rho proteins that acts as a regulator of JAK-STAT and NFκB signalling. We recently found that RhoH controls the expression levels of specific Toll like receptors (TLRs) that act as sensors of microbial components in the innate immune system. By this and other, so far uncharacterised pathways, RhoH expression levels influence TLR-mediated release of inflammatory cytokines from macrophages. It is known that RhoH has an impact on the signalling pathways involving Syk, STATs, NFkB and other Rho GTPases. However, very little is known about the exact molecular mechanisms of these signalling pathways. We aim to understand the mechanism of RhoH-mediated modulation of protein transport and TLR signalling on a molecular level. As a model system we will use bone marrow derived macrophages from wildtype and RhoHdeficient mice. We anticipate the results to be important in order to define mechanisms that might allow manipulating immune cells towards their desired, beneficial function. The project will investigate the regulation of TLR-induced immune signal transduction processes through RhoH leading to cytokine release and cellular functions such as phagocytosis.

RhoH是Rho蛋白家族的造血特异性GTP酶缺陷型成员，作为JAK-STAT和NFκB信号传导的调节剂。我们最近发现，RhoH控制特异性Toll样受体（TLR）的表达水平，这些受体在先天免疫系统中充当微生物组分的传感器。通过这种和其他迄今未表征的途径，RhoH表达水平影响TLR介导的巨噬细胞释放炎性细胞因子。已知RhoH对涉及Syk、STAT、NFkB和其他Rho GTP酶的信号传导途径具有影响。然而，人们对这些信号通路的确切分子机制知之甚少。我们的目的是了解RhoH介导的蛋白质转运和TLR信号转导的分子水平上的调制机制。作为模型系统，我们将使用来自野生型和RhoH缺陷小鼠的骨髓衍生的巨噬细胞。我们预计这些结果对于定义可能允许操纵免疫细胞实现其所需的有益功能的机制非常重要。该项目将研究TLR诱导的免疫信号转导过程的调节，通过RhoH导致细胞因子释放和细胞功能，如吞噬作用。