COOPERATION OF TYROSINE KINASES P72(SYK) AND P53 56(LYN) REGULATES CALCIUM MOBILIZATION IN CHICKEN B-CELL OXIDANT STRESS SIGNALING/

A chicken B cell line DT40 and its syk-negative or lyn-negative mutant s were used to investigate the roles of protein-tyrosine kinases in ox idant stress signaling. The data presented here for wild-type cells de monstrate that hydrogen peroxide stimulates p53/56(lyn)-dependent tyro sine phosphorylation and activation of p72(syk), and induces a rapid a nd prolonged elevation of intracellular calcium, which consists of cal cium release from intracellular stores and influx from the extracellul ar space. Hydrogen-peroxide-triggered calcium mobilization was impaire d in both syk-negative and lyn-negative cells, which was mainly due to the loss of calcium release from intracellular stores. Further studie s indicated that inositol trisphosphate production was also abolished in both syk-negative and lyn-negative cells, which is consistent with the loss of calcium release. Taken together, these observations sugges t that the defect of p72(syk) or p53/56(lyn) was responsible for the a bnormality of calcium mobilization in both lyn-negative and syk-negati ve cells, and that both p72(syk) and p53/56(lyn) might regulate calciu m mobilization through the phosphatidylinositol pathway in B cell oxid ant stress signaling.