Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein.

Bruton's tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase that is crucial for human and murine B cell development, and its deficiency causes human X-linked agammaglobulinemia and murine X-linked immunodeficiency. In this report, we describe the function of the Btk-binding protein Sab (SH3-domain binding protein that preferentially associates with Btk), ...
which we reported previously as a newly identified Src homology 3 domain-binding protein. Sab was shown to inhibit the auto- and transphosphorylation activity of Btk, which prompted us to propose that Sab functions as a transregulator of Btk. Forced overexpression of Sab in B cells led to the reduction of B cell antigen receptor-induced tyrosine phosphorylation of Btk and significantly reduced both early and late B cell antigen receptor-mediated events, including calcium mobilization, inositol 1, 4,5-trisphosphate production, and apoptotic cell death, where the involvement of Btk activity has been demonstrated previously. Together, these results indicate the negative regulatory role of Sab in the B cell cytoplasmic tyrosine kinase pathway.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Apoptosis, B-Lymphocytes, Carrier Proteins, Cell Line, Drosophila, Gene Expression Regulation, Enzymologic, Humans, Kinetics, Mice, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Signal Transduction, Transfection, src Homology Domains
Proc. Natl. Acad. Sci. U.S.A.
Date: May. 25, 1999
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