Receptor-linked protein tyrosine phosphatases (R-PTPs) are a large and diverse group of transmembrane signaling molecules. In Drosophila, four R-PTPs are localized to central nervous system axons in the embryo and may participate in assembly of the central nervous system axon array. In this paper, we identify and characterize a transmembrane glycoprotein, gp150, that selectively interacts with the catalytic domain of the axonal R-PTP DPTP10D. gp150 does not bind to a cysteine-to-serine active site mutant, and binding is inhibited by vanadate, suggesting that it interacts with the active site. It has an extracellular domain composed of 18 leucine-rich repeats, which are found in many adhesion molecules. Its short cytoplasmic domain contains 4 tyrosine residues in sequence contexts that suggest that they could interact with SH2 domain-containing effector molecules. The overall organization of the tyrosine motifs resembles that of antigen recognition activation motif signaling elements from receptors in the vertebrate immune system. The cytoplasmic domain of gp150 is a good substrate for v-Abl tyrosine kinase, and phosphorylated gp150 can be dephosphorylated efficiently in vitro by DPTP10D. We suggest that DPTP10D may function in vivo to regulate phosphorylation of gp150 and thereby control its interactions with downstream effectors.