A taxon-neutral decomposition of the JNK (c-Jun N-terminal kinase) cascade, the stress- and cytokine-activated concrete realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). Environmental stress and inflammatory cytokines signal through upstream MAP3Ks (MEKK1/MAP3K1, ASK1, MLK family) to the dual-specificity MAP2Ks MKK4 (MAP2K4) and MKK7 (MAP2K7), which dually phosphorylate the JNK MAPKs (JNK1/2/3) on their TPY activation-loop motif. Active JNK phosphorylates the transcription factor c-Jun (and JunD, ATF2), assembling the AP-1 transcriptional program that controls stress responses, apoptosis, and proliferation. The kinase relay - MAP3K -> MKK4/7 -> JNK - is declared as an inner bundle that `conforms_to` mapk_relay, while the stress/cytokine input and the JNK/AP-1 output and DUSP-mediated feedback are this cascade's free extensions around the conforming core. Grounded in GO:0007254 (JNK cascade) / GO:0051403 (stress-activated MAPK cascade).
This module is the concrete JNK (stress-activated) branch of the generic three-tier MAP kinase relay (MODULE:mapk_relay): the inner `jnk_relay` node bundles the MAP3K -> MKK4/7 -> JNK tiers and declares conformance to that motif, while the stress/cytokine input step and the downstream JNK/AP-1 output and DUSP-feedback steps are this cascade's free extensions around the conforming core. Representative UniProt members (MEKK1 Q13233, MKK4 P45985, MKK7 O14733, JNK1 P45983) were verified against UniProt.
All recommended fields populated.
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No MODULE:jnk_cascade deep-research report alongside the module YAML.
3 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 |
|---|---|---|---|
| MKK7 (MAP2K7) O14733 | ✗ | — | — |
| JNK1 (MAPK8) P45983 | ✗ | — | — |
| MKK4 (MAP2K4) P45985 | ✗ | — | — |
| MEKK1 (MAP3K1) Q13233 | ✗ | — | — |
Environmental stress (UV, oxidative, heat) and inflammatory cytokines (TNF, IL-1), relayed through MAP4Ks, Rho-family GTPases, and adaptor MAP3Ks, converge to activate the MAP3K tier of the cascade.
Couples stress and cytokine stimuli to the JNK relay.
The three-tier kinase relay of the JNK cascade: a stress-activated MAP3K (MEKK1/ASK1/MLK) phosphorylates MKK4/MKK7 (MAP2K), which dually phosphorylates JNK (MAPK) on its TPY activation-loop motif.
Stress-activated MAP3Ks (MEKK1/MAP3K1, ASK1/MAP3K5, MLK family) phosphorylate and activate MKK4/MKK7.
Top kinase tier; activates MKK4/7.
The dual-specificity MAP2Ks MKK4 (MAP2K4) and MKK7 (MAP2K7) phosphorylate JNK on both threonine and tyrosine of its TPY motif; MKK4 preferentially targets the tyrosine and MKK7 the threonine.
Middle kinase tier; dual-specificity activation of JNK.
Dually phosphorylated JNK1/2/3 (MAPK8/9/10) becomes an active proline-directed serine/threonine kinase acting on cytoplasmic and nuclear substrates.
Effector kinase transducing the stress signal to substrates.
Active JNK phosphorylates the transcription factor c-Jun (and JunD, ATF2), promoting assembly of the AP-1 transcription factor complex and a stress/apoptosis/proliferation gene program.
Converts JNK activity into an AP-1-driven gene program.
DUSP/MKP dual-specificity phosphatases (e.g. DUSP10/MKP-5, DUSP16/MKP-7) dephosphorylate the JNK activation loop to terminate signaling.
Dephosphorylates the JNK activation loop to terminate signaling.