The reversible regulation of phosphotyrosine is essential for translating environmental cues and stresses to responses such as cell adhesion, migration and growth, and is often dysregulated in disease. Central to this regulation is the interplay of kinases and phosphatases (PTPs). Our work is focused on understanding mechanisms of signalling by PTPs. Unlike receptor tyrosine kinases, signalling principles of the type I plasma membrane-localised receptor PTPs remain to be elucidated. Previous work has implicated them as key regulators of growth factor signalling, src family kinases and cell adhesion. In epithelial cells, we have identified substrates and regulated protein-protein interactions for the homophilic receptor PTPRK, as well as surprising non-catalytic tumour suppressor functions. We have now expanded our findings to CD45, a receptor PTP expressed on the surface of all nucleated haematopoietic cells that is required for adaptive immunity. By studying CD45 signalling mechanisms we hope to understand its role in T cell responses to antigen and beyond.