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

(Project leader: Univ.-Prof. Dr. rer. nat., Dipl. Chem. Michael Huber)

Abstract:

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.

SHIP1 is the gatekeeper of mast cell effector functions
(Please klick the images to enlarge them)

SHIP1 and mast cell effector functions
SHIP1 and mast cell effector functions
SHIP1 and mast cell effector functions
Gimborn et al (2005) J Immunol 174:507
Fehrenbach et al (2009) J Immunol 182:7897

Publications

Team:

Univ.-Prof. Dr. rer. nat., Dipl. Chem. Michael Huber
Oindrilla Mukherjee, M.Sc. in Biotechnology, Doktorandin
Thomas Hochdörfer, Dipl. Biol., Doktorand

Contact information:

Biochemie und Molekulare Immunologie, Institut für Biochemie und Molekularbiologie, RWTH Aachen, Universitätsklinikum
Pauwelsstr. 30, 52074 Aachen
Tel.: 0241-80 88837
Fax.: 0241-80 82428
Email: mhuber(at)ukaachen.de
Email: omukherjee(at)ukaachen.de
Email: thochdoerfer(at)ukaachen.de

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