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Biochem Biophys Res Commun. 2012 Jan 6;417(1):5-10. doi: 10.1016/j.bbrc.2011.11.145. Epub 2011 Dec 8.

MEK1/2 dual-specificity protein kinases: structure and regulation.

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  • 1Blue Ridge Institute for Medical Research, Horse Shoe, NC 28742, USA. rrj@brimr.org


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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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