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

Bruton's tyrosine kinase (Btk) is considered an essential signal transducer in B-cells, Mutational defects are associated,with a severe immunodeficiency syndrome, X-chromosome linked agammaglobulinemia (XLA). Here we show by coimmunoprecipitation that a member of the protein kinase C (PKC) family, PKC mu, is constitutively associated with Btk. Neither antigen receptor (Ig) crosslinking nor stimulation of B-cells with phorbol ester or H2O2 affected Btk/PKC mu interaction. GST precipitation analysis revealed association of the Btk pleckstrin/Tec homology domain with PKC mu. Transient over-expression of PKC mu deletion mutants as well as expression of selected PKC mu domains 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. These data shots the existence of a PKC mu/Btk complex in vivo and identify two PKC mu domains that participate in Btk interaction. (C) 1999 Federation of European Biochemical Societies.