Bence K, Ma W, Kozasa T, Huang X Y
Department of Physiology, Cornell University Medical College, New York 10021, USA.
Nature. 1997 Sep 18;389(6648):296-9. doi: 10.1038/38520.
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.
异三聚体鸟嘌呤核苷酸结合调节蛋白(G蛋白)可将来自多种细胞表面受体的信号进行转导,以产生生理反应。蛋白酪氨酸激酶是另一类关键的细胞信号转导分子,其功能异常常导致癌症。虽然G蛋白偶联受体的激活可快速刺激细胞蛋白酪氨酸磷酸化,但G蛋白激活蛋白酪氨酸激酶的机制尚不清楚。在此我们表明,纯化的G蛋白G(q)类的α亚基(G[α]q)可直接刺激纯化的非受体激酶布鲁顿酪氨酸激酶(Btk)的活性,而来自G(i1)、G(O)或G(z)蛋白的纯化α亚基则不能。G(α)q在体内也可激活Btk。此外,在Btk缺陷细胞中,Gq偶联受体对另一种激酶p38丝裂原活化蛋白激酶的刺激被阻断。我们的结果表明,某些蛋白酪氨酸激酶可能是G蛋白的直接效应器。