The ERKs (MAPK p42/p44) are the prototypic MAPKs and are activated by a variety of mitogenic stimuli as well as differentiation signals. MAPK activation largely requires Ras activation. In Drosophila, the ERK homologue is encoded by the Rolled locus (an activated allele) which has been placed downstream of Ras in the sevenless receptor kinase pathway.

ERKs are inactivated by dephosphorylation by specific protein phosphatases such as MKP1 (CL100) and PAC1. Downstream substrates include Elk1, phospholipase A2 and p90Rsk1.

ERK2 is the only enzyme in the family to have its x-ray structure solved.

Erk1/2 in Different Species

Erk1-Mus musculus

Erk1-Rattus norvegicus

Erk1-Homo sapiens

Erk2-Bos taurus

Erk2-Homo sapiens

Erk2-Mus musculus

Erk2-Rattus norvegicus

Erk2-Xenopus laevis

Proteins phosphorylated by Erk1/2

C/EBPalpha -Ser21(inhibition);PMID: 14701740

C/EBPbeta -Thr235(activation);PMID: 20015877

c-Jun - Ser63, Ser73(activation);PMID: 12881422

Elk1 - Ser383, Ser389(activation);PMID: 8262053

Estrogen receptor alpha - Ser104, Ser106 (activation)PMID: 18372406- Ser118 (activation);PMID: 7491495

RGS19 - Ser151(activation)PMID: 10993892

HSF-1 - Ser307(activation)PMID: 8940068

MAPKAPK2 - Ser9, Thr25, Thr222, Ser272, Thr334,Thr338(activation) PMID: 8846784

MBP - Thr94, Thr97(ativation;PMID: 1699809

MEK1 - Thr292 and Thr386(feedback); PMID: 10567369

EIF4EBP1 - Ser264(ativation);PMID: 8083223-Ser209 PMID: 12890645

p90 RSK - Ser363, Thr573(activation);PMID: 10411321

STAT5a -Ser780 (activation);PMID: 10194762

Tyrosine hydroxylase - Ser31(activation);PMID: 1347949

Arachidonate 5-lipoxygenase - Ser664(activation);PMID: 12205041

AEBP1 - Thr623(activation);PMID: 15654748

RUNX1 - Ser249, Ser266 (activation);PMID: 8668214

RSPH3 - Thr286(activation);PMID: 19684019

GRAF - Ser510(activation);PMID: 9525907

GEF-H1 - Thr678(activation);PMID: 18211802

Beta-arrestin-1 - Ser412(activation);PMID: 10347142

ATF-2 - Thr71(activation);PMID: 12110590

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Structure of ERK1 & ERK2

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