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Direct stimulation of Bruton's tyrosine kinase by Gq-protein α-subunit

Author

Listed:
  • Kendra Bence
  • Wei Ma
  • Tohru Kozasa

    (University of Texas Southwestern Medical Center)

  • Xin-Yun Huang

    (Cornell University Medical College)

Abstract

Heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins) transduce signals from a wide variety of cell-surface receptors to generate physiological responses1. Protein-tyrosine kinases are another group of critical cellular signal transducers and their malfunction often leads to cancer2. Although activation of G-protein-coupled receptors can elicit rapid stimulation of cellular protein-tyrosine phosphorylation3, the mechanism used by G proteins to activate protein-tyrosine kinases is unclear. Here we show that the purified α-subunit of the Gq class of G proteins (Gαq) directly stimulates the activity of a purified non-receptor kinase, Bruton's tyrosine kinase (Btk)4, whereas purified α-subunits from Gi1, GO or Gz proteins do not. Gαq can also activate Btk in vivo. Furthermore, in Btk-deficient cells, stimulation of another kinase, a p38 MAP kinase, by Gq-coupled receptors is blocked. Our results demonstrate that certain protein-tyrosine kinases can be direct effectors of G proteins.

Suggested Citation

  • Kendra Bence & Wei Ma & Tohru Kozasa & Xin-Yun Huang, 1997. "Direct stimulation of Bruton's tyrosine kinase by Gq-protein α-subunit," Nature, Nature, vol. 389(6648), pages 296-299, September.
    • Handle: RePEc:nat:nature:v:389:y:1997:i:6648:d:10.1038_38520
    DOI: 10.1038/38520
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