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Ras activation revisited: role of GEF and GAP systems

机译：重新激活Ras：GEF和GAP系统的作用

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Ras is a prototypical small G-protein and a central regulator of growth, proliferation and differentiation processes in virtually every nucleated cell. As such, Ras becomes engaged and activated by multiple growth factors, mitogens, cytokines or adhesion receptors. Ras activation comes about by changes in the steady-state equilibrium between the inactive guanosine diphosphate (GDP)-bound and active guanosine triphosphate (GTP)-bound states of Ras, resulting in the mostly transient accumulation of Ras-GTP. Three decades of intense Ras research have disclosed various families of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) as the two principal regulatory elements of the Ras-GDP/GTP loading status. However, with the possible exception of the GEF Sos, we still have only a rudimentary knowledge of the precise role played by many GEF and GAP members in the signalling network upstream of Ras. As for GAPs, we even lack the fundamental understanding of whether they function as genuine signal transducers in the context of growth factor-elicited Ras activation or rather act as passive modulators of the Ras-GDP/GTP cycle. Here we sift through the large body of Ras literature and review the relevant data for understanding the participation and precise role played by GEFs and GAPs in the process of Ras activation.
机译：Ras是一种典型的小G蛋白，是几乎每个有核细胞中生长，增殖和分化过程的中央调节器。因此，Ras被多种生长因子，有丝分裂原，细胞因子或粘附受体所激活。 Ras活化是通过结合非活性鸟苷二磷酸（GDP）和结合活性鸟苷三磷酸（GTP）的稳态之间的稳态平衡变化引起的，导致Ras-GTP大部分为瞬时积累。三十年来Ras的深入研究已经揭示了鸟嘌呤核苷酸交换因子（GEFs）和GTPase活化蛋白（GAPs）的各种家族，这是Ras-GDP / GTP负载状态的两个主要调控元素。但是，除了GEF Sos可能的例外，我们仍然对许多GEF和GAP成员在Ras上游的信令网络中所起的确切作用仍然只有基本的了解。对于GAP，我们甚至对它们是否在生长因子引起的Ras激活中起真正信号转导器的作用，还是充当Ras-GDP / GTP周期的被动调节剂的作用，甚至缺乏基本的了解。在这里，我们对大量的Ras文献进行了筛选，并回顾了相关数据，以了解GEF和GAP在Ras激活过程中的参与和确切作用。

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