Pleckstrin Homology Domains Interact with Filamentous Actin

• Published in: The Journal of biological chemistry Vol. 274; no. 28; pp. 19752 - 19761
• Main Authors: Yao, L, Janmey, P, Frigeri, L G, Han, W, Fujita, J, Kawakami, Y, Apgar, J R, Kawakami, T
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 09-07-1999
• Subjects: Actins - chemistry; Agammaglobulinaemia Tyrosine Kinase; Amino Acid Sequence; Androstadienes - pharmacology; Animals; Binding Sites; Binding, Competitive; Cytochalasin D - pharmacology; Immunoglobulin E - immunology; Mast Cells - metabolism; Molecular Sequence Data; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphatidylinositol Phosphates - pharmacology; Protein Kinase C - metabolism; Protein-Tyrosine Kinases - chemistry; Rats; Receptors, IgE - metabolism; src Homology Domains; Wortmannin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.28.19752

A fraction of Bruton’s tyrosine kinase (Btk) co-localizes with actin fibers upon stimulation of mast cells via the high affinity
IgE receptor (FcεRI). In this study, a molecular basis of the Btk co-localization with actin fibers is presented. Btk and
other Tec family tyrosine kinases have a pleckstrin homology (PH) domain at their N termini. The PH domain is a short peptide
module frequently found in signal-transducing proteins and cytoskeletal proteins. Filamentous actin (F-actin) is shown to
be a novel ligand for a subset of PH domains, including that of Btk. The actin-binding site was mapped to a 10-residue region
of the N-terminal region of Btk. Basic residues in this short stretch are demonstrated to be involved in actin binding. Isolated
PH domains induced actin filament bundle formation. Consistent with these observations, Btk binds F-actin in vitro and in vivo . Wild-type Btk protein is in part translocated to the cytoskeleton upon FcεRI cross-linking, whereas Btk containing a mutated
PH domain is not. Phosphatidylinositol 3,4,5-trisphosphate-mediated membrane translocation of Btk was enhanced in cytochalasin d -pretreated, FcεRI-stimulated mast cells. These data indicate that PH domain-mediated F-actin binding plays a role in Btk
co-localization with actin filaments.