title: Characterization of the pleckstrin homology domain of Btk as an inositol polyphosphate and phosphoinositide binding domain.
abstract: We previously reported that the pleckstrin homology (PH) domain of Bruton's tyrosine kinase (Btk) binds Ins(1,3,4,5)P4 and that missense mutations in this domain which cause either human X-linked agammaglobulinemia (XLA) or murine X-linked immunodeficiency (Xid) also dramatically reduce the Ins(1,3,4,5)P4 binding activity. In this paper, we describe the inositol phosphate binding specificity of the Btk PH domain and different inositol polyphosphate binding properties among the PH domains of Tec family kinases. Our results suggest that certain inositol phosphates and/or phosphoinositides are physiological ligands of some Tec family kinases and that Tec family members are differently regulated by inositol molecules.
authors.affiliation: Molecular Neurobiology Laboratory, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: F
authors.initials: F
authors.lastname: Hamazato
authors.forename: K
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D007295:Inositol Phosphates / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D010833:Phytic Acid / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010833:Phytic Acid; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; C080813:emt protein-tyrosine kinase