Mediation of PACAPlike neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila
Mediation of PACAPlike neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila
复制标题
果蝇中 Ras/Raf 和 cAMP 信号转导途径共激活介导 PACAP 样神经肽传递
作者：
Y. Zhong
许多关于神经传递的信号转导机制的研究都是针对环AMP和磷酸肌醇途径的作用13。在配体结合后，递质受体与异源三聚体G蛋白相互作用，使Gα和Gβγ亚基解离2，3。然后，游离Gα调节腺苷酸环化酶和磷脂酶C13的活性。已经表明，通过毒蕈碱或神经肽受体激活的Gβγ复合物可以通过激活小鸟嘌呤核苷酸结合蛋白Ras刺激丝裂原活化蛋白激酶（MAPK）4，5。Ras/Raf丝氨酸苏氨酸蛋白激酶/MAPK激酶/MAPK/转录因子途径中的中间体的顺序激活已经成为控制酵母、蠕虫、果蝇和哺乳动物细胞增殖和分化的中心机制611。在这里，我们表明，通过分析果蝇突变体，突触电流和调制的K+电流，触发垂体腺苷酸环化酶激活多肽样neuropeptide 12，介导的Ras/Raf和芸香-agaadenylyl环化酶途径的共激活。因此，Ras/Raf通路似乎也是G蛋白偶联神经传递所必需的。
MUCH work on the signal transduction mechanisms underlying neurotransmission has been directed towards studying the roles of the cyclic AMP and phosphoinositide pathways13. Upon ligand binding, the transmitter receptors interact with heterotrimeric G proteins, allowing Gα and Gβγ subunits to disengage2,3. The free Gα then modulates the activity of adenylyl cyclase and phospholipase C13. It has been suggested that the Gβγ complex which is activated through muscarinic or neuropeptide receptors can stimulate mitogen-activated protein kinase (MAPK) via activation of the small guanine-nucleotide-binding protein Ras4,5. Sequential activation of the intermediates in the Ras/Raf serinethreonine protein kinase/MAPK kinase/MAPK/transcription factor pathway has emerged as a central mechanism for controlling cell proliferation and differentiation in yeast, worms, fruitflies and mammals611. Here we show, by analysis of Drosophila mutants, that synaptic current and modulation of K+ current, triggered by a pituitary adenylyl cyclase-activating polypeptide-like neuropeptide12, are mediated by coactivation of the Ras/Raf and Ruta-agaadenylyl cyclase pathways. Thus the Ras/Raf pathway also appears to be essential for G-protein-coupled neurotransmission.
GAP 结构域负责 ras p21 依赖性毒蕈碱性心房 K 通道电流的抑制。
DOI：
10.1126/science.1553544
发表时间：
1992
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Martin,GA;Yatani,A;Clark,R;Conroy,L;Polakis,P;Brown,AM;McCormick,F
通讯作者：
McCormick,F
cAMP 对钾电流的差异调节及其长期和短期影响：果蝇的 dunce 和 rutabaga 突变体。
影响因子：
1.9
作者：
Zhong,Y;Wu,CF
通讯作者：
Wu,CF