Identification of tyrosine phosphatase ligands for contactin cell adhesion molecules

The incessant tug of war between tyrosine kinases and tyrosine phosphatases regulates critical signaling events during embryogenesis and adulthood. Among these proteins, receptor protein tyrosine phosphatases (RPTPs) have emerged as an important class of neuronal receptors, seemingly capable of mediating cell adhesion and tyrosine dephosphorylation events. Indeed, these proteins combine extracellular domains that resemble those of cell adhesion molecules and tyrosine phosphatase domains that counter the activities of tyrosine kinases. However, the detailed mechanisms underlying RPTP-mediated cell adhesion and RPTP-mediated cell signaling continue to elude our understanding mainly because very few extracellular binding partners of RPTPs have been identified. We have recently characterized biochemically and structurally the interactions between members of the contactin family of neural recognition molecules and the homologous receptor protein tyrosine phosphatase zeta (PTPRZ) and gamma (PTPRG) that are expressed in the nervous system. Here, we present our main findings and we discuss their possible implication for the control of tyrosine dephosphorylation by contactin family members.