RAPID DESENSITIZATION OF B-CELL RECEPTOR BY A DITHIOL-REACTIVE PROTEIN-TYROSINE-PHOSPHATASE INHIBITOR - UNCOUPLING OF MEMBRANE IGM FROM SYKINHIBITS SIGNALS LEADING TO CA2+ MOBILIZATION

B-cell antigen receptor (BCR)-mediated calcium response can be blocked by phenylarsine oxide (PAO), a dithiol group-reactive protein tyrosin e phosphatase inhibitor. We have examined the mechanism of this inhibi tion in BL41 Burkitt lymphoma cells. PAO-dependent inhibition is not r estricted to the BCR-mediated functions, as evidenced by the failure o f the same cells to mobilize Ca2+ in response to CD19 cross-linking. I n contrast, calcium response induced by a putative syk activator, H2O2 , exhibited only a moderate sensitivity to PAO, demonstrating that PAO did not cause general suppression of all the functions leading to Ca2 + mobilization. BCR cross-linking or H2O2 treatment leads to the induc tion of almost complete non-responsiveness for the reciprocal stimulat ion. Since BCR cross-linking did not generate non-responsiveness to H2 O2 in the presence of PAO, and PAO-treated cells remained responsive t o syk activation by H2O2, we suppose that PAO may inhibit BCR-mediated signal transduction events upstream of syk activation. This assumptio n was supported by additional data, indicating that PAO was able to mo dulate functions of at least 2 different protein tyrosine kinase enzym es involved in BCR-mediated signaling. PAO induced rapid and dose-depe ndent tyrosine phosphorylation of lyn and selectively inhibited BCR-me diated tyrosine phosphorylation of syk. The results presented in this paper demonstrate that PAO may provoke cellular desensitization proces s by alteration of the signal transducer functions of lyn and syk tyro sine kinase enzymes.