Protein tyrosine phosphorylation is used extensively to transmit signals that control the growth, proliferation and differentiation of cells. Signaling across the cell membrane is achieved by cell-surface receptors integrated into intracellular phosphorylation and dephosphorylation machineries. Among these receptors, the human receptor protein tyrosine phosphatases (RPTPs) are involved in diverse cellular processes including immune regulation, vascular development and nervous system development. Aberrant expression or mutations of RPTPs have been associated with several human diseases, including proliferative disorders such as cancers. Mutations of RPTPs found in cancer often result in loss of phosphatase activity, suggesting that these genes function as tumor suppressors.
The extracellular domains of RPTPs are comprised mainly of immunoglobulin and fibronectin type III repeats, thus resembling the extracellular domains of cell adhesion molecules. This resemblance ultimately led to the hypothesis that RPTPs could integrate the seemingly disparate functions of cell adhesion and cell signaling. In spite of their role as key regulators of tissue development, the mechanism or mechanisms that regulate the functions of RPTPs are not well understood. My research focuses on establishing the principles that control RPTP-mediated signaling by a combination of biochemical and structural approaches, including X-ray crystallography. This work will provide information on critical aspects of cell signaling and help understand the function of RPTPs in normal and disease states.