Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit.
Heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins) transduce signals from a wide variety of cell-surface receptors to generate physiological responses. Protein-tyrosine kinases are another group of critical cellular signal transducers and their malfunction often leads to cancer. Although activation of G-protein-coupled receptors can elicit rapid stimulation of cellular protein-tyrosine phosphorylation, the mechanism used by G proteins to activate protein-tyrosine kinases is unclear. Here we show that the purified alpha-subunit of the G(q) class of G proteins (G[alpha]q) directly stimulates the activity of a purified non-receptor kinase, Bruton's tyrosine kinase (Btk), whereas purified alpha-subunits from G(il), G(O) or G(z) proteins do not. G(alpha)q 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.
Bence
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Department of Physiology, Cornell University Medical College, New York 10021, USA.
Ma
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Kozasa
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T
Huang
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D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D018411:Spodoptera; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins