Direct inhibition of Bruton's tyrosine kinase by I...[Nat Immunol. 2001]

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1: Nat Immunol. 2001 Oct;2(10):939-46. Links

Comment in:: Nat Immunol. 2001 Oct;2(10):897-8.

Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein.

Liu W, Quinto I, Chen X, Palmieri C, Rabin RL, Schwartz OM, Nelson DL, Scala G.

Department of Clinical and Experimental Medicine, Medical School, University of Catanzaro, 88100 Catanzaro, Italy.

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.

PMID: 11577348 [PubMed - indexed for MEDLINE]

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