Research ArticleDevelopmental Biology

Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect

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Science Signaling  26 Jan 2016:
Vol. 9, Issue 412, pp. ra9
DOI: 10.1126/scisignal.aad5658

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A MEK redundancy threshold

The kinases MEK1 and MEK2 have the same substrates, ERK1 and ERK2, but mice lacking Mek1 die as embryos due to placental defects and mice lacking Mek2 are viable, implying isoform-specific functions. Aoidi et al. determined that MEK1 and MEK2 are functionally redundant as long as sufficient protein is produced. Mice lacking Mek1 were rescued by placing the coding sequence of Mek2 into both alleles of Mek1, but placental defects and embryonic lethality occurred when the mice carried only one copy of this knock-in allele along with a null allele of Mek1. The data indicated that the proteins functionally substituted for one another, but that the developing placenta is particularly sensitive to the amount of MEK present and producing the minimum amount required at least four copies of Mek2 in the absence of Mek1 or two copies of Mek1 in the absence of Mek2. Thus, the products may be functionally identical, but differences in their expression, translation, and protein half-life enable isoform-specific regulation and phenotypes.

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