Transmembrane homodimerization of receptor-like protein tyrosine phosphatases

Receptor-like protein tyrosine phosphatases (RPTPs) are type I integral membrane proteins. Together with protein tyrosine kinases, RPTPs regulate the phosphotyrosine levels in the cell. Studies of two RPTPs, CD45 and PTP alpha, have provided strong evidence that dimerization leads to inactivation of the receptors, and that the dimerization of PTPa involves interactions in the transmembrane domain (TMD). Using the TOX-CAT assail, a genetic approach for analyzing TM interactions in Escherichia coli membranes, we show that the TMD of RPTPs interact in the membrane, albeit to different extents. Using fusion proteins of TMDs, we also observe an equilibrium between monomer and dimer in sodium dodecyl sulfate (SDS) micelles. Through a mutational study of the DEN TMD, we demonstrate that these interactions are specific. Taken together, our results define a subset of the RPTP family in which TM homodimerization may act as a mediator of protein function. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.