 Activated Raf stimulates MAPK-kinase (MAPKK or MEK) by phosphorylating a serine residue in its activation loop.MAPKK then phosphorylates MAPK (ERK1/2) on T and Y residues at the activation-loop leading to its activation.Activated MAPK phosphorylates a variety of cytoplasmic substrates, as well as transcription factors, when translocated into the nucleus.