van Oers, Nicolai S. C.2010-11-022010-11-022008-05-13https://hdl.handle.net/2152.5/805The T cell receptor (TCR) complex consists of the ligand-binding α/β heterodimer as well as four associated signaling chains (CD3 γ, δ, ε, and ζ). Each of the CD3 subunits contains one or more copies of a signaling motif termed an immunoreceptor tyrosine-based activation motif (ITAM). Phosphorylation of tyrosine residues within the ITAMs is critical for TCR-mediated signaling events. We identified an additional signaling motif in the cytoplasmic tail of CD3 ε that we termed the basic-rich stretch (BRS). Biochemical analyses revealed that this motif uniquely interacted with the serine/threonine kinase, G protein-coupled receptor kinase 2 (GRK2). Interactions between the BRS and GRK2 contribute to the ability of the TCR to cross talk with G protein-coupled receptors, such as CXCR4. The BRS was also capable of mediating interactions with certain charged phospholipids. To address the role of the BRS in T cell functions, several murine CD3 ε transgenic lines bearing distinct mutations of the BRS were generated. Analyses of these mice on a CD3 ε null background revealed that modifications of the BRS suppressed T cell development. Taken together, these findings demonstrate that the BRS of CD3 ε plays an important role in TCR signaling and T cell development by regulating unique protein-protein and protein-lipid interactions.Electronicapplication/pdfenGenes, T-Cell ReceptorPhosphorylationReceptor-Interacting Protein Serine-Threonine KinasesThesisborn digital423063850