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

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.

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Teilprojekt zu SPP 1394:  Mast-cells - promoters of health and modulators of disease