Activated RAF proteins are restricted substrate kinases whose primary downstream targets are the two MAP2K proteins, MAPK2K1 and MAP2K2 (also known as MEK1 and MEK2) (reviewed in Roskoski, 2010, Roskoski, 2012a). Phosphorylation of the MAPK2K activation loop primes them to phosphorylate the primary effector of the activated MAPK pathway, the two MAPK proteins MAPK3 and MAPK1 (also known as ERK1 and 2). Unlike their upstream counterparts, MAPK3 and MAPK1 catalyze the phosphorylation of hundreds of cytoplasmic and nuclear targets including transcription factors and regulatory molecules (reviewed in Roskoski, 2012b). Activation of MAP2K and MAPK proteins downstream of activated RAF generally occurs in the context of a higher order scaffolding complex that regulates the specificity and localization of the pathway (reviewed in Brown and Sacks, 2009; Matallanas et al, 2011).
Romano, D, Matallanas, D, Rauch, J, Zebisch, A, Birtwistle, M, Kolch, W, von Kriegsheim, A
Roskoski, R Jr
Brown, MD, Sacks, DB
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