Regulation of the Src-family kinase Lck by posttranslational modifications and TCR/Lck interactions (B19)

• Subject Area: Immunology
• Term: from 2010 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 97850925

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 B19 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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 854: Molecular Organisation of Cellular Communications within the Immune System
• Applicant Institution: Otto-von-Guericke-Universität Magdeburg
• Project Heads: Professor Dr. Wolfgang Schamel; Professor Dr. Burkhart Schraven; Professor Dr. Luca Simeoni