Open AccessBinding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase.
Author(s) -
Satoshi Tsukada,
Melvin I. Simon,
Owen N. Witte,
Arieh A. Katz
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.23.11256
Subject(s) - pleckstrin homology domain , heterotrimeric g protein , bruton's tyrosine kinase , biology , sh3 domain , microbiology and biotechnology , tyrosine kinase , guanine nucleotide exchange factor , proto oncogene tyrosine protein kinase src , biochemistry , signal transduction , g protein
Bruton tyrosine kinase (Btk) has been implicated as the defective gene in both human and murine B-cell deficiencies. The identification of molecules that interact with Btk may shed light on critical processes in lymphocyte development. The N-terminal unique region of Btk contains a pleckstrin homology domain. This domain is found in a broad array of signaling molecules and implicated to function in protein-protein interactions. By using an in vitro binding assay and an in vivo competition assay, the pleckstrin homology domain of Btk was shown to interact with the beta gamma dimer of heterotrimeric guanine nucleotide-binding proteins (G proteins). A highly conserved tryptophan residue in subdomain 6 of the pleckstrin homology domain was shown to play a critical role in the binding. The interaction of Btk with beta gamma suggests the existence of a unique connection between cytoplasmic tyrosine kinases and G proteins in cellular signal transduction.