RAS GTPase proteins activate RAF kinases via dimerization, and the RAF kinases have a restricted substrate specificity to phosphorylate MEK1 and MEK 2 (MEK: MAP/ERK kinase).
The MEK1/2 dual-specificity protein kinases mediate phosphorylation of tyrosine and threonine in ERK1 and ERK2, their only known physiological substrates to date.