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KRAS信號的激活是一個多步驟的過程,需要適當的KRAS翻譯後修飾,細胞膜定位與效應蛋白的相互作用。
The activation of KRAS signaling is a multi-step process that requires proper KRAS post-translation,plasma membrane-localization and interaction with effector proteins.
在細胞外刺激作用下,從失活的RAS-GDP到激活的RAS-GDP的轉化進一步促進了多種信號通路的激活,包括MAPK通路、PI3k 通路和Ral-GEFs通路,其中以MAPK通路的特征最為明顯。
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直接與RAF蛋白結合,將RAF激酶家族從細胞質招募到膜上,在細胞膜上二聚化並活化。激活的RAF隨後對其下遊底物,即MEK and ERk進行一係列磷酸化反應,並傳導生長信號。
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.