Inhibitor Of Bruton Agammaglobulinemia Tyrosine Kinase (IBTK)

High expression of a 7.0-kb IBTK transcript in hemopoietic tissues, but little or no expression in other tissues. Immunoblot analysis showed expression of a 26-kD protein in B-cell lysates. Binding analyses indicated that IBTK associates with the pleckstrin homology domain and BTK motif of BTK in vitro and in vivo. Confocal microscopy demonstrated a diffuse colocalization of IBTK and BTK in discrete cytoplasmic regions, predominantly in the submembrane area after B-cell receptor (BCR) cross-linking. Functional and mutation analyses showed that the C terminus of IBTK mediates the downregulation of BTK kinase activity, interferes with BTK-mediated calcium mobilization induced by BCR triggering, and downregulates the subsequent activation of nuclear factor-kappa-B (NFKB)-driven gene transcription.