New insights into the mechanisms of SOS activation.
New insights into the mechanisms of SOS activation.
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对 SOS 激活机制的新见解。
DOI：
10.1126/stke.4142007pe67
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Quilliam,LawrenceA
中科院分区：
文献类型：
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作者：
Quilliam,LawrenceA
小的鸟苷三磷酸酶Ras的活化对于许多生物事件是至关重要的。因此，普遍表达的Ras鸟嘌呤核苷酸交换因子（GEF）SOS（Son of Sevenless）将蛋白酪氨酸激酶与Ras激活偶联，并处于严格的自抑制控制之下，这并不奇怪。一些研究揭示了多个调控域如何影响SOS活性。最值得注意的是，SOS上的第二个Ras结合位点变构调节Ras激活的持续时间和幅度。这种变构的Ras-GTP由另一种GEF产生，Ras鸟嘌呤核苷酸释放蛋白1（RasGRP 1）。SOS和RasGRP 1都在磷脂酶D2的下游被激活，SOS的功能获得性突变体有助于遗传性疾病。这些研究不仅使我们能够更好地理解GEFs调控的复杂性，而且还促使我们重新评估我们目前对导致Ras激活的途径的理解。
The activation of the small guanosine triphosphatase Ras is critical for many biological events. It is therefore not surprising that the ubiquitously expressed Ras guanine nucleotide exchange factor (GEF) SOS (Son of Sevenless), which couples protein tyrosine kinases to Ras activation, is under tight autoinhibitory control. Several studies have revealed how multiple regulatory domains might affect SOS activity. Most notably, a second Ras-binding site on SOS allosterically regulates the duration and amplitude of Ras activation. This allosteric Ras-GTP is produced by another GEF, Ras guanine nucleotide–releasing protein 1 (RasGRP1). SOS and RasGRP1 are both activated downstream of phospholipase D2, and gain-of-function mutants of SOS contribute to inherited diseases. These studies not only enable us to better appreciate the complexity of the regulation of GEFs but also prompt us to reevaluate our current understanding of pathways that lead to Ras activation.