Characterization of a Novel Signaling Motif in the CD3 ε Subunit of the T Cell Receptor

The 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.

Author dc:creator

• Watts, Laura Michelle

Contributors dc:contributor

• van Oers, Nicolai S. C.

• Genes, T-Cell Receptor
• Phosphorylation
• Receptor-Interacting Protein Serine-Threonine Kinases

Language dc:language

en

Identifier

423063850

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/805