A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal

  • Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling. Here we describe a previously uncharacterized, unexpected role of Mek1 in downregulating Mek2-dependent Erk signaling. Mek1 mediates the regulation of Mek2 in the context of a previously undiscovered Mek1-Mek2 complex. The Mek heterodimer is negatively regulated by Erk-mediated phosphorylation of Mek1 on Thr292, a residue missing in Mek2. Disabling this Erk-proximal negative-feedback step stabilizes the phosphorylation of both Mek2 and Erk in cultured cells and in vivo in Mek1 knockout embryos and mice. Thus, in disagreement with the current perception of the pathway, the role of Mek1 and Mek2 in growth factor-induced Erk phosphorylation is not interchangeable. Our data establish Mek1 as the crucial modulator of Mek and Erk signaling and have potential implications for the role of Mek1 and Mek2 in tumorigenesis.

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Author:Federica Catalanotti, Gloria Ximena Reyes, Veronika Jesenberger, Gergana Galabova-Kovacs, Ricardo de Matos Simoes, Oliviero Carugo, Manuela Baccarini
Parent Title (English):Nat Struct Mol Biol.
Document Type:Article
Language:English
Completed Date:2009/03/16
Date of first Publication:2020/11/27
Responsibility for metadata:Fachhochschule Technikum Wien
Release Date:2020/11/27
GND Keyword:ERK activation; Mek1-Mek2 pathway; cancer biology; tumorigenesis
Volume:2009
Issue:16(3)
First Page:294
Last Page:303
Publish on Website:1
Open Access:0
Reviewed:1
Link to Publication:https://pubmed.ncbi.nlm.nih.gov/19219045/
Department:Department Life Science Engineering
Research Focus:Tissue Engineering & Molecular Life Science Technologies
Projects:Eigenmittel
Studienjahr:2008/2009