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. PANTHER grounding: kinase-tier family descriptors carry family-level PTHR ids checked against interpro/panther membership (PTHR24055 for every MAPK tier, PTHR48013 for all MAP2Ks, including MEK1/MEK2, MKK3/4/5/6/7 and Pbs2/Ste7, per the current PANTHER classification, PTHR24361 for MEKK2/MEKK3). PANTHER subfamilies are deliberately not used: they are not clean paralog groups here (e.g. PTHR48013:SF9, named for MEK5, also contains yeast Ste7 and plant MKKs), so branch identity is carried by the representative members and the PTN evidence rather than by a subfamily id. The stress-activated MAP3K descriptor (MEKK1/ASK1/MLK) spans unrelated PANTHER families and asserts no id.
All recommended fields populated.
✗ none found
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.
4 gene-function check(s) reflected in core functions · 0 conflict(s) · 3 evidence or coverage gap(s) (8 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| jnk_map3k_activity | MEKK1 (MAP3K1) UniProtKB:Q13233 Family Representative |
MAP kinase kinase kinase activity GO:0004709 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| jnk_map2k_activity | MKK4 (MAP2K4) UniProtKB:P45985 Family Representative |
MAP kinase kinase activity GO:0004708 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| jnk_map2k_activity | MKK7 (MAP2K7) UniProtKB:O14733 Family Representative |
MAP kinase kinase activity GO:0004708 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| jnk_mapk_activity | JNK1 (MAPK8) UniProtKB:P45983 Family Representative |
MAP kinase activity GO:0004707 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| jnk_substrate_output | ANY_WITH_FUNCTION Gene |
MAP kinase activity GO:0004707 |
Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews. |
| jnk_map3k_activity | Stress-activated MAP3Ks (MEKK1/ASK1/MLK) Family |
MAP kinase kinase kinase activity GO:0004709 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| jnk_map2k_activity | MKK4/MKK7 (MAP2K4/MAP2K7) PANTHER:PTHR48013 Family |
MAP kinase kinase activity GO:0004708 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR48013. |
| jnk_mapk_activity | JNK MAPKs (MAPK8/9/10) PANTHER:PTHR24055 Family |
MAP kinase activity GO:0004707 |
Family Function Unreviewed
Family review leaves GO:0004707 UNRESOLVED. The cucumber target has a MAP-kinase conserved-site signature, supporting MAPK-type phosphotransfer rather than an arbitrary kinase label. Classical MAPKs and divergent CMGC relatives nevertheless differ in activation-loop regulation and upstream kinases. The complete functional boundary cannot be inferred from a rule-generated catalytic equation or extended to every CMGC-like member without catalytic and activation-mechanism evidence. |
✓ every negative regulator described as feedback has an upstream edge closing the loop.
0 complete review(s) · 4 with deep research · 0 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| MAP2K4 P45985 | ✓ | 41/42 | ✓ |
| MAP2K7 O14733 | ✓ | 53/54 | ✓ |
| MAP3K1 Q13233 | ✓ | 33/34 | ✓ |
| MAPK8 P45983 | ✓ | 150/152 | ✓ |
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. This is modelled as an external input rather than a JNK-driven feedback: the JNK-directed phosphatases represented here are not known to be JNK-induced, and the inducible MKP that also acts on JNK, DUSP1/MKP-1, is expressed under p38/MK2 control rather than by JNK itself, so its induction is cross-regulation from the sibling cascade (see modules/p38_cascade.yaml and the knowledge gap below).
Dephosphorylates the JNK activation loop to terminate signaling.