title: MEK1/2 dual-specificity protein kinases: structure and regulation.
abstract: MEK1 and MEK2 are related protein kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade. This cascade participates in the regulation of a large variety of processes including apoptosis, cell cycle progression, cell migration, differentiation, metabolism, and proliferation. Moreover, oncogenic mutations in RAS or B-RAF are responsible for a large proportion of human cancers. MEK1 is activated by phosphorylation of S218 and S222 in its activation segment as catalyzed by RAF kinases in an intricate process that involves a KSR scaffold. Besides functioning as a scaffold, the kinase activity of KSR is also required for MEK activation. MEK1 regulation is unusual in that S212 phosphorylation in its activation segment is inhibitory. Moreover, active ERK catalyzes a feedback inhibitory phosphorylation of MEK1 T292 that serves to downregulate the pathway.
authors.affiliation: Blue Ridge Institute for Medical Research, Horse Shoe, NC 28742, USA. rrj@brimr.org
authors.forename: Robert
authors.initials: R
authors.lastname: Roskoski
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D004789:Enzyme Activation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D048369:MAP Kinase Kinase 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D011494:Protein Kinases; C097199:KSR-1 protein kinase; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2