Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit
Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit
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DOI：
10.1038/38520
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发表时间：
1997-09-18
期刊：
影响因子：
64.8
通讯作者：
Huang, XY
中科院分区：
文献类型：
--
作者：
Bence, K;Ma, W;Huang, XY
异三聚体鸟嘌呤核苷酸结合调节蛋白(G蛋白)传递来自多种细胞表面受体的信号以产生生理反应(1)。蛋白酪氨酸激酶是另一组关键的细胞信号转导，它们的故障经常导致癌症(2)。虽然G蛋白偶联受体的激活可以快速刺激细胞蛋白酪氨酸磷酸化(3)，但G蛋白激活蛋白酪氨酸激酶的机制尚不清楚。在这里，我们证明了纯化的G(Q)类G蛋白的α亚基(GαQ)直接刺激纯化的非受体蛋白Bruton酪氨酸激酶(BTK)(4)的活性，而来自G(I1)、G(0)或G(Z)蛋白的纯化的α亚基不能，GαQ也可以在体内激活BTK，此外，在BTK缺乏的细胞中，通过GQ偶联受体对另一种激酶-p38 MAP激酶的刺激被阻断。我们的结果表明，某些蛋白酪氨酸激酶可以是G蛋白的直接效应者。
Heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins) transduce signals from a wide variety of cell-surface receptors to generate physiological responses(1). Protein-tyrosine kinases are another group of critical cellular signal transducers and their malfunction often leads to cancer(2). Although activation of G-protein-coupled receptors can elicit rapid stimulation cellular protein-tyrosine phosphorylation(3), 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)(4), whereas purified alpha-subunits from G(i1), G(0) 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 effecters of G proteins.