IL-6 signaling pathway module

IL-6 engages IL6R and gp130/IL6ST receptor complexes, activating JAK kinases and STAT3-centered transcriptional programs that control inflammation, acute-phase responses, and differentiation.

MODULE:il6_signalingDRAFTSignaling Pathwaymodules/il6_signaling.yaml
interleukin-6-mediated signaling pathwayGO:0070102
file:modules/il6_signaling-deep-research-falcon.md
IL-6 signaling pathway Falcon module review
Falcon/Edison module review generated 2026-06-28 is linked as supporting evidence for module boundaries, core mechanism, variation, constraints, and failure modes; open questions in that report require manual review before promotion to curated knowledge gaps.
GO:0070102
interleukin-6-mediated signaling pathway
The module is grounded in the GO biological process term for interleukin-6-mediated signaling pathway.
PANTHER:PTN000140172
PAINT node PTN000140172 for IL6R
Local PAINT IBD node in PTHR23037 with propagated terms F:GO:0019981, P:GO:0070102; PAINT date 20230406.
PANTHER:PTN000210448
PAINT node PTN000210448 for STAT3
Local PAINT IBD node in PTHR11801 with propagated terms C:GO:0005634, C:GO:0005737, F:GO:0000978, F:GO:0000981, P:GO:0006357; PAINT date 20260528.
PANTHER:PTN000210451
PAINT node PTN000210451 for STAT3
Local PAINT IBD node in PTHR11801 with propagated terms P:GO:0019221, P:GO:0043434; PAINT date 20260528.
PANTHER:PTN000210452
PAINT node PTN000210452 for STAT3
Local PAINT IBD node in PTHR11801 with propagated terms C:GO:0090575; PAINT date 20231129.
PANTHER:PTN000927860
PAINT node PTN000927860 for STAT3
Local PAINT IBD node in PTHR11801 with propagated terms P:GO:0007259; PAINT date 20241120.
PANTHER:PTN001562978
PAINT node PTN001562978 for JAK1
Local PAINT IBD node in PTHR45807 with propagated terms F:GO:0004715, P:GO:0007259, P:GO:0019221; PAINT date 20260530.
PANTHER:PTN002521566
PAINT node PTN002521566 for JAK2
Local PAINT IBD node in PTHR45807 with propagated terms P:GO:0060397; PAINT date 20241121.
PANTHER:PTN002623841
PAINT node PTN002623841 for STAT3
Local PAINT IBD node in PTHR11801 with propagated terms P:GO:0033210, P:GO:0060397; PAINT date 20190221.
PANTHER:PTN002745476
PAINT node PTN002745476 for IL6R
Local PAINT IBD node in PTHR23037 with propagated terms C:GO:0043235, F:GO:0004896, F:GO:0019955, P:GO:0019221; PAINT date 20260601.
PANTHER:PTN008588089
PAINT node PTN008588089 for IL6R
Local PAINT IBD node in PTHR23037 with propagated terms P:GO:0008284; PAINT date 20251220.

Curated compact signaling-pathway module generated from verified UniProt exemplar accessions and local PAINT IBD rows. PTN anchors are included only when the exemplar accession appears in an IBD seed row in interpro/panther; roles without local PAINT seeds remain grounded by verified UniProt exemplar accessions. Falcon integration (2026-06-28): Falcon findings are linked as evidence and family-level support. Automatically extracted open-question headings were intentionally not retained as knowledge_gap entries because they were not manually curated. Machine-generated Falcon citations remain curation support and are not manually adjudicated here.

4Nodes
3Parts
0Variant Sets
0Variants
7Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • il6_signaling-deep-research-falcon.md (falcon)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (2/6 grounded genes reviewed)

1 complete review(s) · 2 with deep research · 4 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
JAK1 P23458 ✓ ✓ ✓
JAK2 O60674 ✗ — —
IL6 P05231 ✗ — —
IL6R P08887 ✗ — —
IL6ST P40189 ✗ — —
STAT3 P40763 ✓ 454/456 ✓

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
IL-6 signaling pathwaySignaling Pathwayil6_signaling
interleukin-6-mediated signaling pathwayGO:0070102
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes il6 jak activation.
IL-6 JAK activation leads to stat3 inflammatory output.
Part 1: il6 receptor engagement
IL-6 receptor engagementRegulatory Stepil_6_receptor_engagement

IL6 binds IL6R and recruits IL6ST/gp130 signaling chains.

Annotons

IL-6 cytokine
il6_il_6_cytokine
Participant: Gene Product: IL6
Gene Product:
IL6UniProtKB:P05231

Curated exemplar for the il-6 cytokine role in interleukin-6-mediated signaling pathway.

IL6 receptor alpha
il6r_il6_receptor_alpha
Participant: Family: IL6 receptor alpha family/ortholog group
Family:
IL6 receptor alpha family/ortholog groupPANTHER:PTHR23037
Representative Members: IL6RUniProtKB:P08887

Curated exemplar for the il6 receptor alpha role in interleukin-6-mediated signaling pathway.

gp130 signal transducer
il6st_gp130_signal_transducer
Participant: Family: gp130 signal transducer family/ortholog group
Family:
gp130 signal transducer family/ortholog groupPANTHER:PTHR23037
Representative Members: IL6STUniProtKB:P40189

Curated exemplar for the gp130 signal transducer role in interleukin-6-mediated signaling pathway.

Part 2: il6 jak activation
IL-6 JAK activationRegulatory Stepil_6_jak_activation

gp130-associated JAK kinases activate receptor phosphotyrosine docking sites.

Annotons

JAK1 kinase
jak1_jak1_kinase
Participant: Family: JAK1 kinase family/ortholog group
Family:
JAK1 kinase family/ortholog groupPANTHER:PTHR45807
Representative Members: JAK1UniProtKB:P23458

Curated exemplar for the jak1 kinase role in interleukin-6-mediated signaling pathway.

JAK2 kinase
jak2_jak2_kinase
Participant: Family: JAK2 kinase family/ortholog group
Family:
JAK2 kinase family/ortholog groupPANTHER:PTHR45807
Representative Members: JAK2UniProtKB:O60674

Curated exemplar for the jak2 kinase role in interleukin-6-mediated signaling pathway.

Part 3: stat3 inflammatory output
STAT3 inflammatory outputRegulatory Stepstat3_inflammatory_output

STAT3 relays IL-6 receptor input to acute-phase, survival, and differentiation genes.

Annotons

STAT3 transcription factor
stat3_stat3_transcription_factor
Participant: Family: STAT3 transcription factor family/ortholog group
Family:
STAT3 transcription factor family/ortholog groupPANTHER:PTHR11801
Representative Members: STAT3UniProtKB:P40763

Curated exemplar for the stat3 transcription factor role in interleukin-6-mediated signaling pathway.

gp130 signaling scaffold
il6st_gp130_signaling_scaffold
Participant: Family: gp130 signaling scaffold family/ortholog group
Family:
gp130 signaling scaffold family/ortholog groupPANTHER:PTHR23037
Representative Members: IL6STUniProtKB:P40189

Curated exemplar for the gp130 signaling scaffold role in interleukin-6-mediated signaling pathway.