Interleukin-21 signaling pathway module

Secreted Interleukin-21 (IL21) binds the private alpha receptor subunit IL21R and recruits the shared common gamma chain (IL2RG) to assemble a heterodimeric class I cytokine receptor complex on B cells, T cells, and natural killer (NK) cells. Receptor assembly juxtaposes and activates receptor-associated Janus kinases JAK1 (on IL21R) and JAK3 (on IL2RG), which phosphorylate IL21R cytoplasmic tyrosines (notably Y519) to recruit and phosphorylate STAT3 (and contextually STAT1 and STAT5), driving germinal center B cell differentiation, immunoglobulin class-switch recombination, T follicular helper (Tfh) cell differentiation, and NK/CD8+ T cell effector maturation.

MODULE:il21_signalingDRAFTSignaling Pathwaymodules/il21_signaling.yaml
interleukin-21-mediated signaling pathwayGO:0038114
GO:0038114
interleukin-21-mediated signaling pathway
Grounded in the GO biological process term for interleukin-21-mediated signaling pathway, defined as the series of molecular signals initiated by interleukin-21 binding to its receptor complex (IL21R/IL2RG) on the surface of a target cell.
PMID:11081504
Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.
Identified human IL21 and IL21R as a novel class I four-helix-bundle cytokine-receptor pair that promotes NK cell expansion and regulates B and T lymphocyte proliferation.
PMID:12244150
IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response.
Demonstrated that IL21 induces STAT3 DNA binding and STAT3 tyrosine phosphorylation in human NK and T cells and the NK-92 line (abstract; STAT1 activation by IL21 is documented in Reactome:R-HSA-9006870).
PMID:12504082
Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma-chain.
Established that human IL21 engages the shared cytokine receptor common gamma chain (IL2RG) alongside IL21R to form a functional signaling complex.
PMID:15546387
Biology of IL-21 and the IL-21 receptor.
Review of IL21 as a common gamma-chain family cytokine whose private receptor IL21R activates the JAK-STAT pathway upon ligand binding, with pleiotropic effects on B, T, NK, and dendritic cells (abstract only).
PMID:37339051
A structural blueprint for interleukin-21 signal modulation.
Resolves the structural architecture of the ternary IL21:IL21R:IL2RG signaling complex and defines how ligand geometry controls JAK1/JAK3 juxtaposition and STAT3 vs STAT1 activation amplitude.
Reactome:R-HSA-9005980
IL21 binds IL21R:JAK1
Reactome reaction documenting initial high-affinity binding of secreted IL21 to the IL21R:JAK1 complex at the plasma membrane.
Reactome:R-HSA-9006844
IL21:IL21R:JAK1 binds IL2RG:JAK3
Reactome reaction documenting recruitment of the IL2RG:JAK3 subunit to form the active ternary IL21:IL21R:IL2RG receptor complex.
Reactome:R-HSA-9006850
IL21 receptor JAK phosphorylation
Reactome reaction documenting reciprocal phosphorylation of JAK1 and JAK3 at the activated IL21 receptor complex.
Reactome:R-HSA-9006870
IL21 receptor STAT phosphorylation
Reactome reaction documenting JAK1/JAK3-mediated phosphorylation of STAT3 and STAT1 docked at phosphorylated IL21R.
file:genes/human/IL21/IL21-ai-review.yaml
Human IL21 gene review
Curates human IL21 (UniProtKB:Q9HBE4) with GO:0005125 (cytokine activity) and GO:0038114 (interleukin-21-mediated signaling pathway), upgrading GO:0005126 (cytokine receptor binding) and GO:0005134 (interleukin-2 receptor binding).
file:interpro/panther/PTHR14356/PTHR14356-review.yaml
PANTHER PTHR14356 (INTERLEUKIN-15-RELATED) family review
Documents subfamily partitioning of PTHR14356 into PTHR14356:SF2 (IL21) and PTHR14356:SF3 (IL15), scopes GO:0038114 to subfamily PTHR14356:SF2 (node PTN007637558), and recommends family-wide placement of GO:0005125 (cytokine activity, currently asserted by PAINT only at the IL15 node PTN002682897) at PTN002682898, the node whose seeds span both subfamilies.
PANTHER:PTN002682898
PAINT node PTN002682898 for IL21
Local PAINT IBD node in PTHR14356 (node taxon not recorded in paint.tsv; seeds include IL21 and IL15 orthologs) asserting only biological process terms P:GO:0001819 and P:GO:0050778; PAINT date 20240321.
PANTHER:PTN007637558
PAINT node PTN007637558 for IL21
Local PAINT IBD node in PTHR14356 (node taxon NCBITaxon:117571; seeds are IL21 orthologs only) asserting the single biological process term P:GO:0045954; PAINT date 20240321.
PANTHER:PTN000547990
PAINT node PTN000547990 for IL21R
Local PAINT IBD node in PTHR23037 (node taxon not recorded) asserting C:GO:0009897 (20210917), F:GO:0004896 (20260828), and P:GO:0019221 (20251220); human IL21R (UniProtKB:Q9HBE5) seeds only F:GO:0004896.
PANTHER:PTN002745476
PAINT node PTN002745476 for IL2RG
Local PAINT IBD node in PTHR23037 (node taxon recorded as taxon:2759) asserting C:GO:0005886, C:GO:0043235, F:GO:0004896, F:GO:0019955, and P:GO:0019221 (dates 20230406 to 20260828); human IL2RG (UniProtKB:P31785) seeds all but F:GO:0019955.
PANTHER:PTN008588077
PAINT node PTN008588077 for IL2RG
Local PAINT IBD node in PTHR23037 (node taxon NCBITaxon:117571) asserting C:GO:0005893, F:GO:0015026, P:GO:0030098, P:GO:0035723, P:GO:0038110, P:GO:0038111, and P:GO:0038113 (dates 20250903 to 20260728); human IL2RG (UniProtKB:P31785) seeds all but P:GO:0030098.
PANTHER:PTN001562978
PAINT node PTN001562978 for JAK1 and JAK3
Local PAINT IBD node in PTHR45807 (node taxon NCBITaxon:33213) asserting C:GO:0005829, F:GO:0004715, F:GO:0005126, P:GO:0007259, P:GO:0019221, P:GO:0030154, and P:GO:0035556 (dates 20230112 to 20260828). Human JAK1 (UniProtKB:P23458) seeds F:GO:0004715, P:GO:0007259, and P:GO:0019221; human JAK3 (UniProtKB:P52333) seeds only P:GO:0019221.
PANTHER:PTN000210448
PAINT node PTN000210448 for STAT3 and STAT1
Local PAINT IBD node in PTHR11801 (node taxon NCBITaxon:2759) asserting C:GO:0005634, C:GO:0005737 (20260528), F:GO:0000978 (20251218), F:GO:0000981 (20240729), and P:GO:0006357 (20260828); human STAT3 (UniProtKB:P40763) and STAT1 (UniProtKB:P42224) are seeds for all five.

Three-step JAK-STAT cytokine signaling module modeling Interleukin-21 (subfamily PTHR14356:SF2) signaling through the heterodimeric IL21R (PTHR23037:SF7) and common gamma chain IL2RG (PTHR23037:SF47) receptor complex. Per ligand-in-signaling conventions (projects/LIGANDS_IN_SIGNALING.md), the IL21 ligand annoton uses the subfamily selector PANTHER:PTHR14356:SF2 (because parent family PTHR14356 also contains IL15 in PTHR14356:SF3) and molecular function GO:0005125 (cytokine activity, an is_a child of GO:0048018 receptor ligand activity) rather than receptor-binding terms GO:0005126 or GO:0005134, resolving the Category A gap where GO:0038114 was annotated to IL21R and IL2RG in human GOA but omitted on human IL21. Neither IL21 ligand PAINT node attests a molecular function: PTN002682898 asserts only GO:0001819 and GO:0050778, and PTN007637558 only GO:0045954, all biological process terms; GO:0005125 on the ligand step rests on the IL21 gene review and literature. The IL21R annoton uses the specific GO:0001532 (interleukin-21 receptor activity, an is_a child of GO:0004896); its PAINT node PTN000547990 asserts the parent GO:0004896, a recorded mismatch of specificity. The shared IL2RG chain keeps GO:0004896.

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

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:il21_signaling deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

5 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (14 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.

AnnotonParticipantFunctionAssessment
il21_cytokine_ligand IL21
UniProtKB:Q9HBE4
Family Representative 		cytokine activity
GO:0005125 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
il21r_receptor_alpha IL21R
UniProtKB:Q9HBE5
Family Representative 		interleukin-21 receptor activity
GO:0001532 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
il2rg_common_gamma_chain IL2RG
UniProtKB:P31785
Family Representative 		cytokine receptor activity
GO:0004896 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
jak1_tyrosine_kinase JAK1
UniProtKB:P23458
Family Representative 		non-membrane spanning protein tyrosine kinase activity
GO:0004715 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
jak3_tyrosine_kinase JAK3
UniProtKB:P52333
Family Representative 		non-membrane spanning protein tyrosine kinase activity
GO:0004715 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
stat3_transcription_factor STAT3
UniProtKB:P40763
Family Representative 		DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000981 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
stat1_transcription_factor STAT1
UniProtKB:P42224
Family Representative 		DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000981 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
il21_cytokine_ligand Interleukin-21 cytokine subfamily
PANTHER:PTHR14356:SF2
Family 		cytokine activity
GO:0005125 		Family Supported
Family review supports GO:0005125 FAMILY_WIDE. All members of PTHR14356 (both IL21 in PTHR14356:SF2 and IL15 in PTHR14356:SF3) are secreted four-helix-bundle cytokines that bind and activate class I cytokine receptor complexes.
il21r_receptor_alpha Interleukin-21 receptor subfamily
PANTHER:PTHR23037:SF7
Family 		interleukin-21 receptor activity
GO:0001532 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR23037:SF7.
il2rg_common_gamma_chain Cytokine receptor common subunit gamma subfamily
PANTHER:PTHR23037:SF47
Family 		cytokine receptor activity
GO:0004896 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR23037:SF47.
jak1_tyrosine_kinase Tyrosine-protein kinase JAK1 subfamily
PANTHER:PTHR45807:SF5
Family 		non-membrane spanning protein tyrosine kinase activity
GO:0004715 		Family Supported
Family review supports GO:0004715 FAMILY_WIDE. Shown directly for JAK1, JAK2, JAK3, TYK2 and Hopscotch. The JH1 catalytic site (jh1_ptk_catalytic) is intact in every full-length member checked, so it is core for all four vertebrate subfamilies, the teleost SF2 and hop. It does not apply to the short kinase-domain fragments the HMM also captures in nematodes and fungi. These are not JAKs, and the residue site shows what one of them looks like.
jak3_tyrosine_kinase Tyrosine-protein kinase JAK3 subfamily
PANTHER:PTHR45807:SF3
Family 		non-membrane spanning protein tyrosine kinase activity
GO:0004715 		Family Supported
Family review supports GO:0004715 FAMILY_WIDE. Shown directly for JAK1, JAK2, JAK3, TYK2 and Hopscotch. The JH1 catalytic site (jh1_ptk_catalytic) is intact in every full-length member checked, so it is core for all four vertebrate subfamilies, the teleost SF2 and hop. It does not apply to the short kinase-domain fragments the HMM also captures in nematodes and fungi. These are not JAKs, and the residue site shows what one of them looks like.
stat3_transcription_factor Signal transducer and activator of transcription 3 subfamily
PANTHER:PTHR11801:SF2
Family 		DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000981 		Family Supported
Family review supports GO:0000981 FAMILY_WIDE. Sequence-specific, signal-dependent DNA-binding transcription factor activity is the defining STAT activity and is shown for vertebrate, Drosophila, C. elegans (STA-1) and Dictyostelium STATs, all of which keep the STAT DNA-binding domain. The exceptions are the plant STAT-type linker-SH2 proteins, which lack that domain. C. elegans STA-2 (SF49) is an unresolved case rather than an exception: it regulates antimicrobial-peptide transcription but keeps only the DNA-binding-domain fold, and sequence-specific binding is undemonstrated, so its gene review marks GO:0000978 over-annotated and generalises this term to GO:0140110 transcription regulator activity, without asserting that either is wrong.
stat1_transcription_factor Signal transducer and activator of transcription 1 subfamily
PANTHER:PTHR11801:SF18
Family 		DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000981 		Family Supported
Family review supports GO:0000981 FAMILY_WIDE. Sequence-specific, signal-dependent DNA-binding transcription factor activity is the defining STAT activity and is shown for vertebrate, Drosophila, C. elegans (STA-1) and Dictyostelium STATs, all of which keep the STAT DNA-binding domain. The exceptions are the plant STAT-type linker-SH2 proteins, which lack that domain. C. elegans STA-2 (SF49) is an unresolved case rather than an exception: it regulates antimicrobial-peptide transcription but keeps only the DNA-binding-domain fold, and sequence-specific binding is undemonstrated, so its gene review marks GO:0000978 over-annotated and generalises this term to GO:0140110 transcription regulator activity, without asserting that either is wrong.

Gene-review completeness (5/7 grounded genes reviewed)

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

Gene Review Complete Deep research
IL21 Q9HBE4 ✓ ✓ ✓
JAK1 P23458 ✓ 331/332 ✓
JAK3 P52333 ✓ ✓ ✗
IL2RG P31785 ✗ — —
IL21R Q9HBE5 ✗ — —
STAT1 P42224 ✓ 293/294 ✓
STAT3 P40763 ✓ 454/456 ✓

Details

Context
bony vertebratesNCBITaxon:117571
extracellular regionGO:0005576 plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
Interleukin-21 signaling pathwaySignaling Pathwayil21_signaling
interleukin-21-mediated signaling pathwayGO:0038114
Context
bony vertebratesNCBITaxon:117571
extracellular regionGO:0005576 plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

IL21-induced heterodimerization of IL21R and IL2RG juxtaposes IL21R-associated JAK1 and IL2RG-associated JAK3 for reciprocal trans-phosphorylation and IL21R Y519 phosphorylation.
PMID:15546387
Review stating that IL21R activates the JAK-STAT pathway upon ligand binding.
Reactome:R-HSA-9006850
Reactome reaction documenting reciprocal JAK1/JAK3 phosphorylation in the ternary IL21 receptor complex.
Activated JAK1 and JAK3 phosphorylate STAT3 (on Y705) and STAT1 (on Y701) docked at phosphorylated IL21R, triggering STAT dimerization and nuclear transcriptional activation.
PMID:12244150
IL21 stimulation induces STAT3 tyrosine phosphorylation and DNA binding in human NK and T cells.
Reactome:R-HSA-9006870
Reactome reaction documenting STAT3 and STAT1 phosphorylation at the activated IL21 receptor complex.
Part 1: il21 receptor complex assembly
IL21 engages the heterodimeric IL21R/IL2RG receptor complexRegulatory Stepil21_engages_receptor_complex

Secreted four-helix-bundle cytokine IL21 binds with high affinity to the private alpha chain IL21R and recruits the shared common gamma chain (IL2RG) into a ternary signaling complex at the lymphocyte plasma membrane.

Annotons

IL21 cytokine ligand
il21_cytokine_ligand
Participant: Family: Interleukin-21 cytokine subfamily
Family:
Interleukin-21 cytokine subfamilyPANTHER:PTHR14356:SF2
Representative Members: IL21UniProtKB:Q9HBE4

Function

cytokine activityGO:0005125

Processes

interleukin-21-mediated signaling pathwayGO:0038114

Locations

extracellular regionGO:0005576

Secreted four-helix-bundle cytokine ligand that binds IL21R and recruits IL2RG to initiate the interleukin-21-mediated JAK1/JAK3 signaling cascade.

PMID:11081504
Discovered human IL21 as the secreted cytokine agonist for IL21R on NK, B, and T lymphocytes.
PMID:37339051
Structural blueprint of the ternary IL21:IL21R:IL2RG complex showing how IL21 bridges IL21R and IL2RG.
file:genes/human/IL21/IL21-ai-review.yaml
Human IL21 review curates GO:0005125 (cytokine activity) and GO:0038114 (interleukin-21-mediated signaling pathway) as core functions.
file:interpro/panther/PTHR14356/PTHR14356-review.yaml
PTHR14356 family review scopes GO:0038114 to subfamily PTHR14356:SF2 (PTN007637558) and recommends placing GO:0005125 at PTN002682898, whose seeds span both subfamilies (PAINT currently asserts it only at the IL15 node PTN002682897).
IL21R receptor alpha subunit
il21r_receptor_alpha
Participant: Family: Interleukin-21 receptor subfamily
Family:
Interleukin-21 receptor subfamilyPANTHER:PTHR23037:SF7
Representative Members: IL21RUniProtKB:Q9HBE5

Function

interleukin-21 receptor activityGO:0001532

Processes

interleukin-21-mediated signaling pathwayGO:0038114

Locations

plasma membraneGO:0005886

Private ligand-specific alpha subunit of the IL21 receptor complex that binds IL21, constitutively associates with JAK1 via its intracellular Box1/Box2 motifs, and provides phosphorylated Y519 docking sites for STAT3 and STAT1.

PMID:11081504
Identified IL21R as a lymphoid class I cytokine receptor capable of signal transduction and used it to clone its ligand IL21, supporting interleukin-21 receptor activity (GO:0001532).
PMID:12504082
Biosensor analysis of recombinant ectodomains showed high-affinity IL21 binding to IL21R (KD 70 pM) and ternary complex formation with the common gamma chain.
PMID:15546387
Review stating that IL21R activates the JAK-STAT pathway upon ligand binding.
IL2RG common gamma chain
il2rg_common_gamma_chain
Participant: Family: Cytokine receptor common subunit gamma subfamily
Family:
Cytokine receptor common subunit gamma subfamilyPANTHER:PTHR23037:SF47
Representative Members: IL2RGUniProtKB:P31785

Function

cytokine receptor activityGO:0004896

Processes

interleukin-21-mediated signaling pathwayGO:0038114

Locations

plasma membraneGO:0005886

Shared signaling receptor subunit (gamma-c) recruited to the IL21:IL21R complex that brings associated JAK3 into proximity with IL21R-bound JAK1.

PMID:12504082
Demonstrated direct binding of IL21 to IL2RG and requirement of IL2RG for IL21 signal transduction.
Part 2: jak1 and jak3 kinase activation
JAK1 and JAK3 trans-phosphorylation and receptor phosphorylationRegulatory Stepil21_jak_activation

Juxtaposed JAK1 (on IL21R) and JAK3 (on IL2RG) trans-phosphorylate and phosphorylate cytoplasmic tyrosine residues on IL21R (principally Y519), creating SH2 docking sites for STAT3 and STAT1.

Annotons

JAK1 non-receptor tyrosine kinase
jak1_tyrosine_kinase
Participant: Family: Tyrosine-protein kinase JAK1 subfamily
Family:
Tyrosine-protein kinase JAK1 subfamilyPANTHER:PTHR45807:SF5
Representative Members: JAK1UniProtKB:P23458

Function

non-membrane spanning protein tyrosine kinase activityGO:0004715

Locations

cytosolGO:0005829 plasma membraneGO:0005886

IL21R-associated Janus kinase activated upon ternary complex assembly to phosphorylate IL21R cytoplasmic tyrosines and docked STAT3/STAT1 transcription factors.

PMID:15546387
Review stating that the private receptor IL21R activates the JAK-STAT pathway upon ligand binding (abstract; JAK1 activation specifically is documented in Reactome:R-HSA-9006850).
Reactome:R-HSA-9006870
Reactome reaction for JAK1/JAK3-mediated STAT phosphorylation at the activated IL21 receptor complex.
JAK3 non-receptor tyrosine kinase
jak3_tyrosine_kinase
Participant: Family: Tyrosine-protein kinase JAK3 subfamily
Family:
Tyrosine-protein kinase JAK3 subfamilyPANTHER:PTHR45807:SF3
Representative Members: JAK3UniProtKB:P52333

Function

non-membrane spanning protein tyrosine kinase activityGO:0004715

Locations

cytosolGO:0005829 plasma membraneGO:0005886

IL2RG-associated Janus kinase that trans-activates with JAK1 upon IL21-induced receptor heterodimerization to drive STAT3 and STAT1 phosphorylation.

PMID:15546387
Review placing IL21 in the common gamma-chain cytokine family whose private receptor IL21R activates JAK-STAT signaling (abstract; JAK3 activation by the IL21 receptor complex is documented in Reactome:R-HSA-9006850).
Reactome:R-HSA-9006850
Reactome reaction documenting reciprocal phosphorylation of JAK1 and JAK3 in the IL21 receptor complex.
Part 3: stat3 and stat1 transcriptional output
STAT3 and STAT1 nuclear translocation and transcriptional outputRegulatory Stepil21_stat_transcriptional_output

Tyrosine-phosphorylated STAT3 (the dominant effector) and STAT1 dimerize, translocate to the nucleus, and activate target genes (including BCL6, PRDM1/BLIMP1, IFNG, and GZMB) that govern germinal center B cell differentiation, immunoglobulin production, Tfh differentiation, and lymphocyte cytotoxicity.

Annotons

STAT3 transcription factor
stat3_transcription_factor
Participant: Family: Signal transducer and activator of transcription 3 subfamily
Family:
Signal transducer and activator of transcription 3 subfamilyPANTHER:PTHR11801:SF2
Representative Members: STAT3UniProtKB:P40763

Function

DNA-binding transcription factor activity, RNA polymerase II-specificGO:0000981

Locations

cytosolGO:0005829 nucleusGO:0005634

Primary transcriptional effector of IL21 signaling that docks at phosphorylated IL21R Y519, is phosphorylated on Y705 by JAK1/JAK3, and drives B cell plasma cell differentiation, Tfh generation, and humoral immunity.

PMID:12244150
Demonstrated IL21-induced STAT3 DNA binding and STAT3 tyrosine phosphorylation in human NK and T cells.
PMID:37339051
Demonstrated that STAT3 is the most potent and sustained signaling output of the IL21:IL21R:IL2RG receptor complex.
STAT1 transcription factor
stat1_transcription_factor
Participant: Family: Signal transducer and activator of transcription 1 subfamily
Family:
Signal transducer and activator of transcription 1 subfamilyPANTHER:PTHR11801:SF18
Representative Members: STAT1UniProtKB:P42224

Function

DNA-binding transcription factor activity, RNA polymerase II-specificGO:0000981

Locations

cytosolGO:0005829 nucleusGO:0005634

Secondary transcriptional effector activated by IL21/IL21R/IL2RG that promotes IFNG and T-bet (TBX21) expression in T and NK cells and balances STAT3-driven transcriptional programs.

PMID:12244150
IL21 up-regulates IFNG and other innate immunity and Th1 genes in human T and NK cells (abstract reports STAT3, not STAT1; STAT1 activation is documented in Reactome:R-HSA-9006870).
PMID:37339051
Engineered IL21 variants reveal differential tuning of STAT1 versus STAT3 phosphorylation downstream of IL21R/IL2RG.