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KRAS信号的激活是一个多步骤的过程,需要适当的KRAS翻译后修饰,细胞膜定位与效应蛋白的相互作用。
The activation of KRAS signaling is a multi-step process that requires proper KRAS post-translation,plasma membrane-localization and interaction with effector proteins.
在细胞外刺激作用下,从失活的RAS-GDP到激活的RAS-GDP的转化进一步促进了多种信号通路的激活,包括MAPK通路、PI3k 通路和Ral-GEFs通路,其中以MAPK通路的特征最为明显。
In response to extracellular stimuli, the conversion from inactive RAS-GDP to active RAS-GDP further promotes the activation of various signaling pathways, which includes MAPK pathway,PI3k pathway and the Ral-GEFs pathway,among them the MAPK pathway is the best characterized.
RAS-GDP直接与RAF蛋白结合,将RAF激酶家族从细胞质招募到膜上,在细胞膜上二聚化并活化。激活的RAF随后对其下游底物,即MEK and ERk进行一系列磷酸化反应,并传导生长信号。
RAS-GDP directly binds to RAF protein,recruiting RAF Kinese family from cytoplasm to membranes,where they dimerize and become active. The activated RAF subsequently carries out a chain of phospholation reactions to its downstream substrates, MEK and ERk, and propagates the growth signal.