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 PTPα, have provided strong evidence that dimerization leads to inactivation of the receptors, and that the dimerization of PTPα involves interactions in the transmembrane domain (TMD). Using the TOXCAT assay, 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 DEP1 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.
Bibliographical noteFunding Information:
We thank Erin Matthews for the advice on protein purification and members of the Engelman lab for careful reading of the manuscript. J.N.S. is supported by NRSA Grant (GM071134-02). This work is supported by grants from the NIH (GM54160 and GM070895) and NFCR (National Foundation for Cancer Research).