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Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit

K Bence1, W Ma, T Kozasa

  • 1Department of Physiology, Cornell University Medical College, New York 10021, USA.

Nature
|September 26, 1997
PubMed

Insights

G proteins are key cell signalers. This study shows that the G(alpha)q protein directly activates Bruton

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • G proteins and protein-tyrosine kinases are crucial signal transducers in cells.
  • G protein-coupled receptor activation stimulates protein-tyrosine phosphorylation, but the mechanism is unknown.
  • Dysfunctional protein-tyrosine kinases are linked to cancer development.

Purpose of the Study:

  • To elucidate the mechanism by which G proteins activate protein-tyrosine kinases.
  • To determine if specific G protein subunits directly interact with and activate protein-tyrosine kinases.

Main Methods:

  • Purified alpha-subunits of different G protein classes were used to test for direct kinase activation.
  • In vitro kinase assays were performed with purified Bruton's tyrosine kinase (Btk).
  • In vivo experiments assessed G(alpha)q activation of Btk and downstream signaling in Btk-deficient cells.

Main Results:

  • The purified G(alpha)q subunit directly stimulated the activity of purified Bruton's tyrosine kinase (Btk).
  • Other G protein alpha-subunits (G[alpha]il, G[alpha]o, G[alpha]z) did not activate Btk.
  • G(alpha)q activated Btk in vivo, and this activation was essential for p38 MAP kinase stimulation by Gq-coupled receptors in Btk-deficient cells.

Conclusions:

  • Certain protein-tyrosine kinases, like Btk, are direct downstream effectors of specific G proteins, such as G(alpha)q.
  • This finding reveals a novel direct signaling pathway linking G proteins to protein-tyrosine kinase activation.
  • The G protein-tyrosine kinase interaction has implications for understanding cellular signaling and disease pathogenesis.

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