Bruton's tyrosine kinase (Btk) associates with protein kinase C mu

Bruton's tyrosine kinase (Btk) is considered an essential signal transducer in B-cells, Mutational defects are associated,with a severe immunodeficien cy syndrome, X-chromosome linked agammaglobulinemia (XLA). Here we show by coimmunoprecipitation that a member of the protein kinase C (PKC) family, P KC mu, is constitutively associated with Btk. Neither antigen receptor (Ig) crosslinking nor stimulation of B-cells with phorbol ester or H2O2 affecte d Btk/PKC mu interaction. GST precipitation analysis revealed association o f the Btk pleckstrin/Tec homology domain with PKC mu. Transient over-expres sion of PKC mu deletion mutants as well as expression of selected PKC mu do mains in 293T cells revealed that both the kinase domain and the regulatory C1 region are independently capable of binding to the Btk PH-TH domain. Th ese data shots the existence of a PKC mu/Btk complex in vivo and identify t wo PKC mu domains that participate in Btk interaction. (C) 1999 Federation of European Biochemical Societies.