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. Author manuscript; available in PMC: 2017 Dec 5.
Published in final edited form as: Adv Exp Med Biol. 2017;963:337–358. doi: 10.1007/978-3-319-50044-7_20

Figure 1. Primary structure of ERK5 and its regulation by shear stress.

Figure 1

A. ERK5 is twice the size of other MAPKs and hence the largest kinase within its group. It possesses a catalytic N-terminal domain including the MAPK-conserved threonine/glutamic acid/tyrosine (TEY) motif in the activation loop with 50% homology with ERK1/2, and a unique C-terminal tail including transactivation domains. The activation of ERK5 occurs via interaction with and dual phosphorylation in its TEY motif by MEK. On the other hand, inflammatory stimuli or athero-prone flow (d-flow) leads to ERK5 deactivation via phosphorylation of Ser486 or Ser496, respectively. The N-terminus K6 and K22 sites with small ubiquitin-like modifier (SUMO) modification inhibit its own transactivation. B. After ERK5 kinase activation induced by MEK5 binding or athero-protective flow (s-flow) stimulation and TEY motif phosphorylation with de-SUMOylation, ERK5 transcriptional activity at the C-terminus region is fully activated. In contrast, d-flow increases ERK5 SUMOylation and ERK5 Ser496 phosphorylation and inhibits ERK5 transcriptional activity. eNOS, endothelial nitric oxide synthesase; KLF, Kruppel-like factor; p90RSK, p90 ribosomal S6 kinase; PKCζ, protein kinase C-ζ; and PPAR, peroxisome proliferator-activated receptor. Reprinted and modified from Heo et al(Heo et al., 2016) with permission of the publisher..