Project Details
Projekt
Genetische Analyse des Mechanismus der ubiquitinilierungsabhängigen Kontrolle der Signaltransduktion durch den T-Zell Rezeptor (The genetic analysis of the mechanism of the ubiquitination-dependent control of T cell receptor signalling)
Applicant
Professor Dr. Alexander Tarakhovsky
Subject Area
Biochemistry
Term
from 1998 to 2003
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5106079
The development and activation of T cells is governed by signals derived from T cell antigen receptor. Binding of the MHCpeptide ligands to TCR and CD4 or CD8 co-receptors induces the activation of src-family protein tyrosine kinase (src-PTK) followed by assembly of the functional TCR-dependent signal transducing chain. The strength of the TCR dependent signal is largely detemined by the surface expression levels of TCR-CD3 signalling complex and intracellular expression levels of src-PTK Lck and Fyn. Binding of the MHC-peptide ligand to TCR is followed by ubiquitination and down-regulation of TCR-CD3 and srcPTKs. This process is supposed to play an important role in setting up the threshold for T cell activation at levels preventing the hyperactivation of T cells. The mechanisms of ligand-induced ubiquitination of TCR and src-PTKs are poorly understood. The aim of the proposed project is to understand the mechanism of ubiquitination of TCR-CD3 and src-PTK and the role of this process in T cell activation and development.
DFG Programme
Priority Programmes
