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

Receptor protein tyrosine phosphatase rho (RPTPp/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 PTP kappa, PTP mu and PCP-2. Glutathione-S-transferase (GST) pulldown assays were used to show that RPTP rho interacts with several adherens junctional proteins in brain, including E-cadherin, N-cadherin, VE-cadherin (cadherin-5), desmoglein, alpha, beta and gamma catenin, p120(ctn) and alpha-actinin. With the exception of E-cadherin and alpha-actinin, binding was considerably reduced at high sodium concentrations. Furthermore, immunoprecipitation phosphatase assays indicated that E-cadherin, and to a far lesser extent p120(ctn), were tyrosine dephosphorylated by a recombinant RPTP rho intracellular fragment, and thus, were likely to be primary substrates for RPTP rho. The interaction of RPTP rho 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. (c) 2006 Elsevier B.V. All rights reserved.