ACTIVATION OF BTK BY A PHOSPHORYLATION MECHANISM INITIATED BY SRC FAMILY KINASES

Bruton's tyrosine kinase (BTK) is pivotal in B cell activation and dev elopment through its participation in the signaling pathways of multip le hematopoietic receptors. The mechanisms controlling BTK activation were studied here by examination of the biochemical consequences of an interaction between BTK and SRC family kinases. This interaction of B TK with SRC kinases transphosphorylated BTK on tyrosine at residue 551 , which led to BTK activation. BTK then autophosphorylated at a second site. The same two sites were phosphorylated upon B cell antigen rece ptor cross-linking. The activated BTK was predominantly membrane-assoc iated, which suggests that BTK integrates distinct receptor signals re sulting in SRC kinase activation and BTK membrane targeting.