ERK1 and ERK2 present functional redundancy in tetrapods despite higher evolution rate of ERK1

BMC Evolutionary Biology
Roser BuscàPhilippe Lenormand

Abstract

The Ras/Raf/MEK/ERK signaling pathway is involved in essential cell processes and it is abnormally activated in ~30 % of cancers and cognitive disorders. Two ERK isoforms have been described, ERK1 and ERK2; ERK2 being regarded by many as essential due to the embryonic lethality of ERK2 knock-out mice, whereas mice lacking ERK1 are viable and fertile. The controversial question of why we have two ERKs and whether they have differential functions or display functional redundancy has not yet been resolved. To investigate this question we used a novel approach based on comparing the evolution of ERK isoforms' sequences and protein expression across vertebrates. We gathered and cloned erk1 and erk2 coding sequences and we examined protein expression of isoforms in brain extracts in all major clades of vertebrate evolution. For the first time, we measured each isoforms' relative protein level in phylogenetically distant animals using anti-phospho antibodies targeting active ERKs. We demonstrate that squamates (lizards, snakes and geckos), despite having both genes, do not express ERK2 protein whereas other tetrapods either do not express ERK1 protein or have lost the erk1 gene. To demonstrate the unexpected squamates' lack of ERK2 ex...Continue Reading

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Citations

Jul 5, 2016·Frontiers in Cell and Developmental Biology·Roser BuscàPhilippe Lenormand
Nov 21, 2012·PloS One·Mariana B GrizanteTiana Kohlsdorf
Jul 26, 2016·Frontiers in Cell and Developmental Biology·Marc K Saba-El-LeilSylvain Meloche
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Methods Mentioned

BETA
FCS
transfections
Fluorescence
transfection
electrophoresis
PCR

Software Mentioned

BioNJ
Selecton
BLAST
MEGA
Cn3D
ProtTest
SeaView
Linux
Ensembl

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