Activated Ras then activates the protein kinase activity of a RAF kinase. The RAF kinase phosphorylates and activates a MAPK/ERK Kinase (MEK1 or MEK2). The MEK phosphorylates and activates a mitogen-activated protein kinase (MAPK).
RAF and MAPK/ERK are both serine/threonine-specific protein kinases. MEK is a serine/tyrosine/threonine kinase.
In a technical sense, RAF, MEK, and MAPK are all mitogen-activated kinases, as is MNK (see below). MAPKs were originally called "extracellular signal-regulated kinases" (ERKs) and "microtubule associated protein kinases" (MAPKs). One of the first proteins known to be phosphorylated by ERK was a microtubule-associated protein (MAP). As discussed below, many additional targets for phosphorylation by MAPK were later found, and the protein was renamed "mitogen-activated protein kinase" (MAPK). The series of kinases from RAF to MEK to MAPK is an example of a protein kinase cascade. Such series of kinases provide opportunities for feedback regulation and signal amplification.