ACTIVATION OF TSK AND BTK TYROSINE KINASES BY G-PROTEIN BETA-GAMMA-SUBUNITS

Tsk/Itk and Btk are members of the pleckstrin-homology (PH) domain-con taining tyrosine kinase family. The PH domain has been demonstrated to be able to interact with beta gamma subunits of heterotrimeric guanin e nucleotide-binding proteins (G proteins) (G(beta gamma)) and phospho lipids. Using cotransfection assays, we show here that the kinase acti vities of Tsk and Btk are stimulated by certain G(beta gamma) subunits . Furthermore, using an in vitro reconstitution assay with purified bo vine brain G(beta gamma) subunits and the immunoprecipitated Tsk, we f ind that Tsk kinase activity is increased by G(beta gamma) subunits an d another membrane factor(s). These results indicate that this family of tyrosine kinases could be an effector of heterotrimeric G proteins.