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

Authors: Roskoski R, JR 
Citation: Roskoski R Jr Biochem Biophys Res Commun. 2012 Jan 6;417(1):5-10. Epub 2011 Dec 8.
Pubmed: (View Article at PubMed) PMID:22177953
DOI: Full-text: DOI:10.1016/j.bbrc.2011.11.145

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.


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CRRD Object Information
CRRD ID: 5686410
Created: 2012-01-23
Species: All species
Last Modified: 2012-01-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.