title: Bruton's tyrosine kinase (Btk) associates with protein kinase C mu.
abstract: 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, PKCmu, is constitutively associated with Btk. Neither antigen receptor (Ig) crosslinking nor stimulation of B-cells with phorbol ester or H(2)O(2) affected Btk/PKCmu interaction. GST precipitation analysis revealed association of the Btk pleckstrin/Tec homology domain with PKCmu. Transient overexpression of PKCmu deletion mutants as well as expression of selected PKCmu 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 show the existence of a PKCmu/Btk complex in vivo and identify two PKCmu domains that participate in Btk interaction.
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. franz-josef.johannes@po.uni-stuttgart.de
authors.forename: F J
authors.initials: FJ
authors.lastname: Johannes
authors.forename: A
authors.initials: A
authors.lastname: Hausser
authors.forename: P
authors.initials: P
authors.lastname: Storz
authors.forename: L
authors.initials: L
authors.lastname: Truckenmüller
authors.forename: G
authors.initials: G
authors.lastname: Link
authors.forename: T
authors.initials: T
authors.lastname: Kawakami
authors.forename: K
authors.initials: K
authors.lastname: Pfizenmaier
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D002460:Cell Line; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D014162:Transfection
chemical_list: D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D005982:Glutathione Transferase; C089212:protein kinase D; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D011493:Protein Kinase C