The inositol phosphatase SHIP1 as the regulator of the physiological mast cell response

肌醇磷酸酶 SHIP1 作为生理肥大细胞反应的调节剂

• 批准号: 124579250
• 负责人: Professor Dr. Michael Huber
• 金额: --
• 依托单位: Institut für Biochemie und Molekulare Immunologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/124579250?language=en
• 关键词: inositol; phosphatase; SHIP1; regulator; physiological

Absence of adequate regulation is a prerequisite for pathophysiological developments, like hypersensitivity reactions and cancer. Thus, comprehension of physiological reactions requires knowledge about their regulation. In previous years, we were able to work out the central role which is played by the inositol-5-phosphatase, SHIP1, in regulating appropriate mast cell (MC) responses. If SHIP1 is missing, MCs severely hyper-react in response to diverse stimuli, like allergens, growth factors, and bacterial constituents. So far, this cellular behavior was explained mainly by SHIP1´s catalytic function. However, in addition to its catalytic domain SHIP1 possesses various structural possibilities to interact with other proteins (i. e. an adaptor function). To understand how SHIP1 is controlling the physiological activation of MCs and why SHIP1 deficiency is resulting in hyperreactivity of MCs, we will, in this proposed project, thoroughly analyze the structural characteristics of SHIP1 and correlate them to SHIP1´s distinct functions.

缺乏适当的调节是病理生理发展的先决条件，如超敏反应和癌症。因此，理解生理反应需要了解它们的调节。在过去的几年中，我们能够找出肌醇-5-磷酸酶，SHIP 1，在调节适当的肥大细胞（MC）的反应中发挥的核心作用。如果SHIP 1缺失，MC会对各种刺激（如过敏原、生长因子和细菌成分）产生严重的过度反应。到目前为止，这种细胞行为主要由SHIP 1的催化功能来解释。然而，除了其催化结构域之外，SHIP 1还具有与其他蛋白质相互作用的各种结构可能性（即，e.适配器功能）。为了了解SHIP 1如何控制MCs的生理激活以及为什么SHIP 1缺乏会导致MCs的高反应性，我们将在这个拟议的项目中彻底分析SHIP 1的结构特征，并将其与SHIP 1的独特功能相关联。

项目成果

Secretory lysosomes of mouse mast cells store and exocytose active caspase‐3 in a strictly granzyme B dependent manner

小鼠肥大细胞的分泌溶酶体以严格依赖颗粒酶 B 的方式储存和胞吐活性 caspaseâ3

• DOI: 10.1002/eji.201343941
• 发表时间: 2013
• 期刊: European Journal of Immunology
• 影响因子: 5.4
• 作者: Martin