Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein.
Bruton's tyrosine kinase (Btk) is required for human and mouse B cell development. Btk deficiency causes X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency in mice. Unlike Src proteins, Btk lacks a negative regulatory domain at the COOH terminus and may rely on cytoplasmic Btk-binding proteins to regulates its kinase ... activity by trans-inhibitor mechanisms. Consistent with this possibility, IBtk, which we identified as an inhibitor of Btk, bound to the PH domain of Btk. IBtk downregulated Btk kinase activity, Btk-mediated calcium mobilization and nuclear factor-kappaB-driven transcription. These results define a potential mechanism for the regulation of Btk function in B cells.
Mesh Terms:
Amino Acid Sequence, B-Lymphocytes, Calcium, Carrier Proteins, Cell Line, Humans, Molecular Sequence Data, NF-kappa B, Protein-Tyrosine Kinases, RNA, Messenger, Tissue Distribution, Transcription, Genetic, Two-Hybrid System Techniques
Amino Acid Sequence, B-Lymphocytes, Calcium, Carrier Proteins, Cell Line, Humans, Molecular Sequence Data, NF-kappa B, Protein-Tyrosine Kinases, RNA, Messenger, Tissue Distribution, Transcription, Genetic, Two-Hybrid System Techniques
Nat. Immunol.
Date: Oct. 01, 2001
PubMed ID: 11577348
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