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PMID: 7972043 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 23 ·1994-11-08 ·Pages 11256-60

Tsukada S, Simon MI, Witte ON, Katz A

Abstract

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.

Related Genes
btk
MeSH Terms
Agammaglobulinaemia Tyrosine Kinase Amino Acid Sequence Animals Blood Proteins/chemistry Cyclic AMP-Dependent Protein Kinases/metabolism GTP-Binding Proteins/metabolism Macromolecular Substances Mice Molecular Sequence Data Phosphoproteins Protein Binding Protein-Tyrosine Kinases/chemistry,metabolism Sequence Alignment Sequence Homology, Amino Acid Signal Transduction Structure-Activity Relationship Tryptophan/chemistry beta-Adrenergic Receptor Kinases
Chemicals
Blood Proteins Macromolecular Substances Phosphoproteins platelet protein P47 Tryptophan Protein-Tyrosine Kinases Agammaglobulinaemia Tyrosine Kinase BTK protein, human Btk protein, mouse Cyclic AMP-Dependent Protein Kinases beta-Adrenergic Receptor Kinases GTP-Binding Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tsukada S
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1662.
Simon M I
Witte O N
Katz A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.23.11256
Published
1994-11-08
Pages
11256-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45206
Subset
IM
Grants
NCI NIH HHS · CA12800 · United States
NIGMS NIH HHS · GM 34236 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.23.11256 PMC Full Text View journal details
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