Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPρ/PTPRT)

Receptor protein tyrosine phosphatase rho (RPTPρ/PTPRT) is a transmembrane protein that is highly expressed in the developing and adult central nervous system. It is a member of the RPTP R2B subfamily, which includes PTPκ, PTPμ and PCP-2. Glutathione-S-transferase (GST) pulldown assays were used to show that RPTPρ interacts with several adherens junctional proteins in brain, including E-cadherin, N-cadherin, VE-cadherin (cadherin-5), desmoglein, α, β and γ catenin, p120ctn and α-actinin. With the exception of E-cadherin and α-actinin, binding was considerably reduced at high sodium concentrations. Furthermore, immunoprecipitation phosphatase assays indicated that E-cadherin, and to a far lesser extent p120ctn, were tyrosine dephosphorylated by a recombinant RPTPρ intracellular fragment, and thus, were likely to be primary substrates for RPTPρ. The interaction of RPTPρ with adherens junctional components suggests that this phosphatase may transduce extracellular signals to the actin cytoskeleton and thereby play a role in regulating cadherin-mediated cell adhesion in the central nervous system.