BAP-135, a target for Bruton's 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 protein, BAP-135, that is associated with Btk in B cells and is a substrate for phosphorylation by Btk. BAP-135, which exhibits no detectable homology to known proteins, contains six occurrences of a hitherto undescribed amino acid repeat and two motifs, similar to the Src autophosphorylation site, that represent potential targets for tyrosine phosphorylation. The pleckstrin homology domain of Btk comprises the principal 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 receptor (BCR) engagement; in response to BCR crosslinking, BAP-135 is transiently phosphorylated on tyrosine. Taken together, these observations suggest that BAP-135 may reside downstream of Btk in a signaling pathway originating at the BCR.
Yang
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Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D016384:Consensus Sequence; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D015398:Signal Transduction; D019473:Transcription Factors, TFII
C104259:GTF2I protein, human; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D019473:Transcription Factors, TFII; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human