Direct stimulation of bruton's tyrosine kinase by gq-protein α-subunit

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. Access through your institution Buy or subscribe This is a preview of subscription content, access

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Download references ACKNOWLEDGEMENTS We thank M. Stieger for plasmid pREP4groESL; T. Kurosaki for Btk-deficient DT40 cells; P. Low for plasmic pCDB3/T7-7; and L. Levin, T. Maack, C. Malbon

and members of our laboratory for reading the manuscript. Part of the Sf9 cells were cultured in the National Cell Culture Center which is supported by the National Center for Research

Resources. This work was supported by grants from the NIH, the NSF and the American Heart Association. X-Y.H. is a Cornell Scholar and a Beatrice F. Parvin Investigator of the American Heart

Association New York City affiliate. AUTHOR INFORMATION Author notes * Kendra Bence, Wei Ma and Xin-Yun Huang: These authors contributed equally to this work. * Xin-Yun Huang:

Correspondence and requests for materials should be addressed to X.-Y.H. AUTHORS AND AFFILIATIONS * Department of Physiology, Cornell University Medical College, 1300 York Avenue, New York,

10021, New York, USA Xin-Yun Huang * Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75235, Texas, USA Tohru Kozasa Authors * Kendra Bence View author

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AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bence, K., Ma, W., Kozasa, T. _et al._ Direct stimulation of Bruton's tyrosine kinase by Gq-protein

α-subunit. _Nature_ 389, 296–299 (1997). https://doi.org/10.1038/38520 Download citation * Received: 02 June 1997 * Accepted: 20 June 1997 * Issue Date: 18 September 1997 * DOI:

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