A taxon-neutral decomposition of the ERK5 (big MAP kinase 1, BMK1) cascade, the MEF2-driven concrete realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). Growth factors, and oxidative and osmotic stress, signal through the MAP3Ks MEKK2 (MAP3K2) and MEKK3 (MAP3K3) to the dedicated dual-specificity MAP2K MEK5 (MAP2K5), which dually phosphorylates the MAPK ERK5 (MAPK7) on its TEY activation-loop motif. ERK5 is distinctive in carrying a large C-terminal transcriptional-activation domain in addition to its kinase domain, and its principal output is activation of MEF2-family transcription factors controlling proliferation, survival, and endothelial/cardiovascular development. The kinase relay - MEKK2/3 -> MEK5 -> ERK5 - is declared as an inner bundle that `conforms_to` mapk_relay, while the upstream input and the ERK5/MEF2 output are this cascade's free extensions around the conforming core. Grounded in GO:0070375 (ERK5 cascade).
This module is the concrete ERK5 branch of the generic three-tier MAP kinase relay (MODULE:mapk_relay): the inner `erk5_relay` node bundles the MEKK2/3 -> MEK5 -> ERK5 tiers and declares conformance to that motif, while the upstream input and the downstream ERK5/MEF2 output are this cascade's free extensions around the conforming core. Representative UniProt members (MEKK3 Q99759, MEKK2 Q9Y2U5, MEK5 Q13163, ERK5 Q13164) were verified against UniProt.
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No MODULE:erk5_cascade deep-research report alongside the module YAML.
2 leaf node(s) with no concrete protein grounding:
✓ every declared conforms_to bundle matches its template motif.
0 complete review(s) · 0 with deep research · 4 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| MEK5 (MAP2K5) Q13163 | ✗ | — | — |
| ERK5 (MAPK7) Q13164 | ✗ | — | — |
| MEKK3 (MAP3K3) Q99759 | ✗ | — | — |
| MEKK2 (MAP3K2) Q9Y2U5 | ✗ | — | — |
Growth factors (EGF, neurotrophins) and oxidative/osmotic stress, relayed through receptor tyrosine kinases and upstream regulators, converge to activate the MEKK2/MEKK3 MAP3K tier of the cascade.
Couples growth-factor and stress stimuli to the ERK5 relay.
The three-tier kinase relay of the ERK5 cascade: MEKK2/MEKK3 (MAP3K) phosphorylate MEK5 (MAP2K), which dually phosphorylates ERK5 (MAPK) on its TEY activation-loop motif.
The MAP3Ks MEKK2 (MAP3K2) and MEKK3 (MAP3K3) phosphorylate and activate MEK5.
Top kinase tier; activates MEK5.
The dual-specificity MAP2K MEK5 (MAP2K5) phosphorylates ERK5 on both threonine and tyrosine of its TEY motif.
Middle kinase tier; dual-specificity activation of ERK5.
Dually phosphorylated ERK5 (MAPK7) becomes an active proline-directed serine/threonine kinase; its large C-terminal domain also provides intrinsic transcriptional-activation function.
Effector kinase transducing the cascade output to MEF2.
Active ERK5 phosphorylates and co-activates MEF2-family transcription factors (MEF2A/C/D), driving proliferation, survival, and endothelial/cardiovascular gene programs.
Converts ERK5 activity into a MEF2-driven gene program.