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, 1Btk, which we identified as an inhibitor of Btk, bound to the PH domain of Btk. 1Btk downregulated Btk kinase activity, Btk-mediated calcium mobilization and nuclear factor-κB-driven transcription. These results define a potential mechanism for the regulation of Btk function in B cells.

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

PALMIERI C;QUINTO I;SCALA G
2001-01-01

Abstract

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, 1Btk, which we identified as an inhibitor of Btk, bound to the PH domain of Btk. 1Btk downregulated Btk kinase activity, Btk-mediated calcium mobilization and nuclear factor-κB-driven transcription. These results define a potential mechanism for the regulation of Btk function in B cells.
2001
Bruton's tyrosine kinase ; X-linked agammaglobulinemia; B cell
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/2743
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