B 19 - Regulation of the Src-family kinase Lck by posttranslational modifications and TCR/Lck interactions

The tyrosine kinase Lck phosphorylates the immunoreceptor tyrosine based signaling motifs (ITAMS) of the T cell receptor (TCR) and, hence, is crucial for T cell activation. Lck enzymatic activity is regulated by post-translational modifications and Lck conformational dynamics. Results of the 2nd funding period and data from the Schamel group (Freiburg) support a new model for the initiation of TCR triggering in which ligand-induced “TCR-opening” induces de novo activation of Lck, thereby facilitating ITAM phosphorylation. Using novel biochemical, microscopy, cellular and mouse models B 19 will assess the mechanistic aspects of how the TCR and Lck cooperate for signal initiation and how new post-translational modifications regulate Lck’s activity.