P72SYK TYROSINE KINASE IS ACTIVATED BY OXIDIZING CONDITIONS THAT INDUCE LYMPHOCYTE TYROSINE PHOSPHORYLATION AND CA2+ SIGNALS

We have used H2O2 as a pharmacologic agent to examine the effects of o xidizing conditions on lymphocyte signal pathways. Treatment of Ramos cells with 5-10 mM H2O2 gave rapid and strong tyrosine phosphorylation of multiple cellular proteins and activation of p72syk to levels equa l to or greater than that observed upon surface Ig cross-linking. Stro ng Ca2+ signals that could be blocked by the tyrosine kinase inhibitor herbimycin A were also observed under these conditions. However, ther e was no increase in activity for the Src family kinases p56lck, p59fy n, or p56/p53lyn. Our findings that the p72syk tyrosine kinase respond s to H2O2 treatment of cells suggest that this kinase is likely to con tribute to cellular tyrosine phosphorylation and calcium signaling ind uced by oxidizing conditions. Furthermore, H2O2 may be useful as a pha rmacologic agent to distinguish the effects of p72syk-related kinases from those of Src family kinases.