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.
Publications
- Oindrilla Mukherjee, Lars Weingarten, Inken Padberg, Catrin Pracht, Rileen Sinha, Thomas Hochdörfer, Stephan Kuppig, Rolf Backofen, Michael Reth, Michael Huber:
The SH2-domain of SHIP1 interacts with the SHIP1 C-terminus: Impact on SHIP1/Ig-α interaction. Biochimica et Biophysica Acta, 1812 (2012), 206-214, Elsevier. - Thomas Hochdörfer, Marcel Kuhny, Carolin N. Zorn, Rudi W. Hendriks, Bart Vanhaesebroeck, Thomas Bohnacker, Gerald Krystal, Michael Huber:
Activation of the PI3K pathway increases TLR-induced TNF-α and IL-6 but reduces IL-1β production in mast cells. Cellular Signalling 23 (2011), 866-875, Elsevier.
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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