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

缺乏适当的调节是病理生理发展的先决条件，如过敏反应和癌症。因此，理解生理反应需要了解它们的调节。在过去的几年里，我们能够找出肌醇-5-磷酸酶SHIP1在调节适当的肥大细胞（MC）反应中所起的核心作用。如果SHIP1缺失，MCs对各种刺激，如过敏原、生长因子和细菌成分，会产生严重的过度反应。到目前为止，这种细胞行为主要由SHIP1的催化功能来解释。然而，除了它的催化结构域，SHIP1还具有与其他蛋白质相互作用的各种结构可能性（即适配器功能）。为了了解SHIP1如何控制MCs的生理激活，以及SHIP1缺陷导致MCs高反应性的原因，我们将在本项目中深入分析SHIP1的结构特征，并将其与SHIP1的不同功能联系起来。

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.