CELL-CELL ADHESION MEDIATED BY A RECEPTOR-LIKE PROTEIN-TYROSINE-PHOSPHATASE

Receptor-like protein tyrosine phosphatases (receptor-PTPs) represent a novel family of transmembrane proteins that are thought to play impo rtant roles in cellular regulation. They consist of a cytoplasmic cata lytic region, a single transmembrane segment and an extracellular, put ative ligand-binding domain, hut the nature of their physiological lig ands is unknown. We have recently cloned a new receptor-PTP (RPTPmu), the ectodomain of which includes an Ig-like and four fibronectin type III-like domains, suggesting that RPTPmu may be involved in cell-cell or cell-matrix interactions. To test this hypothesis, we expressed RPT Pmu in insect Sf9 cells using recombinant baculovirus. We demonstrate that RPTPmu dramatically promotes cell-to-cell adhesion in a homophili c, Ca2+-independent manner. No adhesion is observed in Sf9 cells expre ssing a chimeric RPTPmu molecule containing the extracellular domain o f the epidermal growth factor receptor. Furthermore, cells expressing an enzymatically inactive, point-mutated RPTPmu or a truncated form of RPTPmu, lacking the entire catalytic region, show adhesive properties indistinguishable from those of wild-type RPTPmu, indicating that the catalytic domain is not essential for RPTPmu-mediated adhesion. These results assign a physiological role for RPTPmu in signaling cell-cell recognition.