BAP-135, A TARGET FOR BRUTONS TYROSINE KINASE IN RESPONSE TO B-CELL RECEPTOR ENGAGEMENT

Bruton's tyrosine kinase (Btk) is essential for B cell activation, but downstream targets of Btk have not been defined. We now describe a pr otein, BAP-135, that is associated with Btk in B cells and is a substr ate for phosphorylation by Btk. BAP-135, which exhibits no detectable homology to known proteins, contains six occurrences of a hitherto und escribed amino acid repeat and two motifs, similar to the Src autophos phorylation site, that represent potential targets for tyrosine phosph orylation. The pleckstrin homology domain of Btk comprises the princip al site of BAP-135; binding, Btk-dependent phosphorylation of BAP-135 is abolished by mutations that impair activation of Btk by Src-related kinases. Btk and BAP-135 exist in a complex before B cell antigen rec eptor (BCR) engagement; in response to BCR crosslinking, BAP-135 is tr ansiently phosphorylated on tyrosine, Taken together, these observatio ns suggest that BAP-135 may reside downstream of Btk in a signaling pa thway originating at the BCR.