Here, we review mechanisms of Ras spatiotemporal clustering with PI3Kα and Raf at the membrane. The large RTK‒Ras‒PI3Kα lipid kinase assembly is at the membrane to generate signaling lipid PIP3. Raf, but not PI3Kα, has long linker extending from the membrane to the kinase domain. This disordered linker stretches into the cytoplasm where Raf's kinase domain side-to-side dimerization and activation is allosterically-driven by MEK under KSR dimers control. The cytoplasm, but not the crowded membrane surface, can accommodate the large Raf's activation and MAPK signaling assemblies, and Raf's disordered linker brings them there. Further, Raf's activation, but not PI3Kα's, requires kinase domain dimerization; Ras nanoclusters accomplishing this necessitate Raf's long linkers. Thus, biophysical and functional constraints shape Ras spatiotemporal assemblies.

中文翻译：

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膜上的Ras组件和信号。

在这里，我们审查与膜PI3Kα和Raf的Ras时空聚集的机制。大的RTK‒Ras‒PI3Kα脂质激酶组件在膜上产生信号脂质PIP3。Raf而非PI3Kα具有从膜延伸至激酶结构域的长接头。这种无序的接头延伸到细胞质中，在KSR二聚体的控制下，MEK以别构方式驱动Raf的激酶结构域并排二聚化和激活。细胞质可容纳较大的Raf活化和MAPK信号传导组件，但不能容纳拥挤的膜表面，Raf的无序接头将其带到那里。此外，Raf的活化而不是PI3Kα的活化需要激酶结构域二聚化。Ras纳米簇完成了此任务，因此需要Raf的长连接子。从而，