We are interested in the molecular events that follow activation of T cells via the T cell antigen receptor (TCR). TCR stimulation triggers several events including activation of protein tyrosine kinases (PTKs), phosphorylation of multiple protein substrates and formation of signaling complexes. Using signaling molecules tagged with GFP analogs investigators in the lab have observed the rapid formation of signaling clusters composed of multi-molecular signaling complexes at the site of TCR engagement.

One of the molecules recruited to signaling clusters and of great interest to the lab is LAT. LAT plays a central role in T cell activation downstream of the TCR by directly or indirectly recruiting kinases, effectors and adaptors to facilitate signal transduction pathways. In addition, we have demonstrated that LAT is ubiquitinated and that LAT ubiquitination is a molecular checkpoint for attenuation of T cell signaling. We are interested in investigating the mechanism by which LAT ubiquitination regulates T cell signaling. Furthermore, to investigate the role of LAT ubiquitination in vivo, we have generated transgenic mice expressing WT and ubiquitin-defective 2KR LAT in postthymic mature T cells. We want to evaluate whether enhanced signaling in cells expressing ubiquitination-resistant LAT will augment responses to pathogens or tumor.