UC San Diego

Fibrosis is a condition characterized by tissue overgrowth, hardening, and /or scarring. It is typically caused by excess deposition of extracellular matrix (ECM) components. Fibroblasts play an important role in the maintenance and reabsorption of the ECM, and thus can be critical mediators of the condition. Protein Tyrosine Phosphatase Receptor Type Gamma (PTPRG) is highly expressed in fibroblasts, and so we want to delve into how PTPRG activation and inactivation may play a role in the condition. The phosphatase activity of receptor-type protein tyrosine phosphatases (RPTPs) is widely thought to be regulated through dimerization, however, the dimerization of PTPRG in fibroblast activity has not been seen in primary cells. Thus, we used FRET microscopy on a primary PTPRG knockout murine dermal fibroblast cell line (mDF) transfected with PTPRG mutant constructs to observe full-length protein dimerization in a cellular context. We also performed biochemical observations of protein activity through phosphatase activity experiments. We found that WT and several mutants of PTPRG dimerize in mDFs. A dimerization-inactivating mutant exhibits less dimerization in cells and in vitro.