UC San Diego

T-cell protein tyrosine phosphatase (TCPTP) is a classical non-transmembrane PTP that is expressed in every cell, despite its name. In its catalytic domain, it shares 65% similarity identity to PTP1B, which was the first tyrosine phosphatase to be identified, and the most thoroughly researched. Based on its similarity with PTP1B, TCPTP is predicted to have a 280 amino acid catalytic domain followed by the regulatory α helix 7 (α7), and a C-terminal intrinsically disordered region. Allosteric inhibitors that target α7 and the C-terminal tail of PTP1B have been characterized. Since the active sites of classical PTPs have generally similar features, targeting the active site leads to inhibitors with poor specificity. Therefore, domains that regulate the PTP catalytic activity have been the focus of much recent research. In this study, we will be investigating the role of the C-terminal domain of TCPTP. The regulation of TCPTP by the C-terminal domain are not clearly defined. By knocking out TCPTP and reconstituting the wild-type full length and catalytic domain, we will assess the effect of the C-terminal domain on TCPTP activity in a cellular context. By combining mutagenesis, enzymatic assays, and FRET assays, we will investigate the areas in the protein and mechanisms that are responsible for its inhibition and activation in cells and in vitro.