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Published November 8, 1994 | Published
Journal Article Open

Binding of βγ subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase


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 βγ 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 βγ suggests the existence of a unique connection between cytoplasmic tyrosine kinases and G proteins in cellular signal transduction.

Additional Information

© 1994 National Academy of Sciences. Contributed by Melvin I. Simon, July 25, 1994. We thank Yuko Kawakami and Toshiaki Kawakami for helpful discussions. We thank Dr. Robert J. Lefkowitz for his generous gift of the DNA construct encoding the C-terminal 222 aa of βARK1 fused to GST and Julia Shimaoka for preparation of the manuscript. O.N.W. is an Investigator with the Howard Hughes Medical Institute. This work was supported by the Howard Hughes Medical Institute and National Institutes of Health Grant CA12800 to O.N.W. and by National Institutes of Health Grant GM 34236 to M.I.S. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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August 20, 2023
August 20, 2023