TEMPORAL DIFFERENCES IN THE ACTIVATION OF 3 CLASSES OF NONTRANSMEMBRANE PROTEIN-TYROSINE KINASES FOLLOWING B-CELL ANTIGEN RECEPTOR SURFACE ENGAGEMENT

We evaluated in WEHI 231 B cells the time-dependent responses of Lyn, Blk, Btk, Syk, and three members of the Jak family of protein tyrosine kinases following antibody-mediated surface engagement of the B-cell antigen receptor. Our results show that the enzyme activities of Lyn a nd Blk were stimulated within seconds of antigen receptor engagement a nd correlated with the initial tyrosine phosphorylation of the Ig alph a and Ig beta subunits of the B-cell antigen receptor. Btk enzyme acti vity was also transiently stimulated and was maximal at approximate to 5 min after B-cell receptor surface binding. Syk activity gradually i ncreased to a maximum at 10-30 min following receptor ligation and was found to parallel the association of Syk with the tyrosine phosphoryl ated Ig alpha and Ig beta subunits of the receptor. While the specific activities of the Jak1, Jak2, and Tyk2 protein tyrosine kinases were unaltered following B-cell receptor ligation, the abundance of Jak1 an d Jak2 were increased 3- to 4-fold within 10 min of receptor engagemen t. These results demonstrate that multiple families of nontransmembran e protein tyrosine kinases are temporally regulated during the process of B-cen antigen receptor-initiated intracellular signal transduction .