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In typical ERK1/2 pathways, ligand-induced activation of receptor tyrosine kinases (RTKs) at the plasma membrane activates and recruits the small GTPase RAS in its GTP-bound form, which then triggers dimerization and activation of MAP3K RAF to initiate a downstream phosphorylation cascade for sequential activation of MAP2K MEK and MAPK ERK (Lavoie and Therrien 2015)