HOMOPHILIC BINDING OF PTP-MU, A RECEPTOR-TYPE PROTEIN-TYROSINE-PHOSPHATASE, CAN MEDIATE CELL-CELL AGGREGATION

The receptor-like protein tyrosine phosphatase, PTPmu, displays struct ural similarity to cell-cell adhesion molecules of the immunoglobulin superfamily. We have investigated the ability of human PTPmu to functi on in such a capacity. Expression of PTPmu, with or without the PTPase domains, by recombinant baculovirus infection of Sf9 cells induced th eir aggregation. However, neither a chimeric form of PTPmu, containing the extracellular and transmembrane segments of the EGF receptor and the intracellular segment of PTPmu, nor the intracellular segment of P TPmu expressed as a soluble protein induced aggregation. PTPmu mediate s aggregation via a homophilic mechanism, as judged by lack of incorpo ration of uninfected Sf9 cells into aggregates of PTPmu-expressing cel ls. Homophilic binding has been demonstrated between PTPmu-coated fluo rescent beads (Covaspheres) and endogenously expressed PTPmu on MvLu c ells. Additionally the PTPmu-coated beads specifically bound to a bact erially expressed glutathione-S-transferase fusion protein containing the extracellular segment of PTPmu (GST/PTPmu) adsorbed to petri dishe s. Covaspheres coated with the GST/PTPmu fusion protein aggregated in vitro and also bound to PTPmu expressed endogenously on MvLu cells. Th ese results suggest that the ligand for this transmembrane PTPase is a nother PTPmu molecule on an adjacent cell. Thus homophilic binding int eractions may be an important component of the function of PTPmu in vi vo.