CSF2RB

UniProt ID: P32927
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

CSF2RB encodes the shared transmembrane beta chain of the human GM-CSF, interleukin-3 and interleukin-5 receptors. It cooperates with ligand-specific alpha chains to form cytokine-binding receptor assemblies, stabilize high-affinity interactions and couple extracellular engagement to associated JAKs and intracellular signaling proteins. This supports cytokine-dependent survival, proliferation and activation of hematopoietic cells. The beta chain has no intrinsic kinase domain. Disrupted receptor function can impair pulmonary surfactant homeostasis and is associated with pulmonary alveolar proteinosis. Two sequence-defined products differ by a six-residue insertion in the extracellular region; their functional equivalence has not been established.

Proposed New Ontology Terms

granulocyte-macrophage colony-stimulating factor binding

Definition: Binding to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Justification: Preserve the distinct GM-CSF ligand identity of an existing experimentally supported binding assertion. The current cytokine-binding child audit finds IL-3, IL-5 and G-CSF binding terms, whereas GO:0042021 explicitly names a GM-CSF complex. Resolve whether that existing term should be clarified or a separate ligand-binding term is needed; no autonomous beta-only binding or new process is asserted.

Parent term: cytokine binding

Supporting Evidence:

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004896 cytokine receptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: The shared beta chain contributes cytokine recognition and transmembrane signaling.
Reason: The actual PTHR23037 v19 target sequence and tree place human CSF2RB below PTN000547990, which carries the exact cytokine-receptor IBD. Receptor reconstitution, beta-chain mutagenesis and ligand-contact experiments support a performed contribution to cytokine recognition and transmembrane signaling in the assembled receptor. Neither cytokine receptor activity nor its signaling-receptor parent requires a single chain to function in isolation. This source assertion remains biologically correct; the compact core separately records the cooperative activity as a contribution. The coreceptor refinement on the broader signaling-receptor row describes the shared-beta role more specifically and does not reject receptor function or infer intrinsic kinase activity.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000547990 SUPPORTS TRANSFER
Actual cytokine-receptor IBD on the authenticated P32927 target path; the broad activity agrees with independent beta-chain experiments.
GO:0004896 cytokine receptor activity
IEA
GO_REF:0000002
ACCEPT
Summary: The mapped cytokine-receptor activity is consistent with the beta-chain role.
Reason: The cytokine-receptor family mapping agrees with direct beta-chain ligand contacts and transmembrane signaling through assembled alpha/beta receptors. Broad electronic coverage can be retained without asserting isolated beta-only function or intrinsic kinase activity. The accepted cytokine-specific activity and the role-specific coreceptor refinement of the broader signaling-receptor assertion are compatible: coreceptor activity is itself a signaling-receptor activity. The compact core records the contribution to the assembled cytokine-receptor activity; the literal source relationship is preserved.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR003531 SUPPORTS TRANSFER
The actual InterPro record maps to broad cytokine receptor activity, consistent with the cooperative target function.
InterPro:IPR011365 SUPPORTS TRANSFER
The actual InterPro record maps to broad cytokine receptor activity, consistent with the cooperative target function.
GO:0004912 interleukin-3 receptor activity
TAS
PMID:9410898
Human pulmonary alveolar proteinosis associated with a defec...
ACCEPT
Summary: CSF2RB contributes to IL-3 receptor activity within the assembled receptor.
Reason: Preserve the existing contributes_to assertion. The full human PAP paper reports beta-chain expression and GM-CSF/IL-3 response defects and describes shared receptor composition. Its IL-3 contribution is compatible with the separately read direct receptor-assembly literature; this is not an isolated beta-chain signaling assay.
GO:0004914 interleukin-5 receptor activity
TAS
PMID:9410898
Human pulmonary alveolar proteinosis associated with a defec...
ACCEPT
Summary: CSF2RB contributes to IL-5 receptor activity within the assembled receptor.
Reason: Preserve contributes_to. The clinical source describes the established shared IL-5 receptor role rather than performing a new IL-5 signaling reconstitution. Actual human IL-5 receptor binding/assembly experiments and later structural work corroborate that contribution.
GO:0005515 protein binding
IPI
PMID:1495999
Molecular basis of the membrane-anchored and two soluble iso...
MODIFY
Summary: The assembled beta-containing receptor contacts IL-5.
Reason: The original human IL-5 receptor paper crosslinks radiolabeled IL-5 to the beta chain in COS-1 cells coexpressing alpha and beta and measures increased affinity (Figure 5). Refine to IL-5 binding at receptor-assembly scope; do not claim beta alone binds the ligand or infer downstream phosphorylation from this paper. The independently read human ectodomain structure in PMID:38614096 also places IL-5R alpha and beta on opposite sides of an IL-5 helical bundle; its tagged/zippered complex is not an assay of isolated full-length beta affinity.
Proposed replacements: interleukin-5 binding
Supporting Evidence:
PMID:1495999
a 2-fold increase in binding affinity
PMID:38614096
IL-5RΞ± and Ξ²c bind on either side
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005515 protein binding
IPI
PMID:1495999
Molecular basis of the membrane-anchored and two soluble iso...
MODIFY
Summary: CSF2RB associates with the IL-5 receptor alpha chain.
Reason: The original coexpression, ligand-crosslinking and affinity experiments support beta association with the IL-5 receptor alpha chain in the assembled receptor. The literal receptor-binding definition fits this partner class; it does not imply that beta is a secreted ligand or that the experiment is a purified binary binding measurement.
Proposed replacements: interleukin-5 receptor binding
Supporting Evidence:
PMID:1495999
Coexpression of the hIL5R beta chain
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005515 protein binding
IPI
PMID:16437163
Growth factor pleiotropy is controlled by a receptor Tyr/Ser...
MODIFY
Summary: CSF2RB associates with a protein tyrosine kinase, with the original figure scope distinguished.
Reason: JAK2 is a nonreceptor protein tyrosine kinase, making GO:1990782 more informative than generic binding. The literal MINT record points to Figure 2D of PMID:16437163; that caption separates receptor immunoprecipitates from cell-lysate phospho-JAK2 blots and does not by itself establish pairwise contact. The receptor–JAK2 coimmunoprecipitation in PMID:17828305 Figure 2b independently supports the association, also consistent with PMID:18692472. This refinement neither makes CSF2RB a kinase nor claims purified binary binding. GO:0030971 receptor tyrosine kinase binding would misclassify JAK2. PMID:38614096 reports strongest beta association with JAK1 and additional JAK2/TYK2 association in tagged HeLa receptor micropatterning using JAK FERM–SH2 constructs. This assay-specific ranking does not establish a universal native JAK hierarchy or negate the original JAK2 association.
Proposed replacements: protein tyrosine kinase binding
Supporting Evidence:
PMID:17828305
required for the recruitment and phosphorylation of Janus kinase-2
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005515 protein binding
IPI
PMID:17828305
CBAP interacts with the un-liganded common beta-subunit of t...
KEEP AS NON CORE
Summary: CBAP/TMEM102 associates with the unliganded beta-chain cytoplasmic region.
Reason: PMID:17828305 identifies CBAP using the CSF2RB box-2 region in yeast two-hybrid assays and reports GST confirmation and endogenous TF-Bcl2 coimmunoprecipitation. Association increases during GM-CSF withdrawal. These positive interaction data are retained under the standing binding policy; CBAP overexpression/knockdown and the proposed apoptogenic receptor-complex model do not establish a more precise CSF2RB molecular activity. The study distinguishes predominant intracellular vesicular pools from a detectable surface pool, rather than excluding interaction by compartment expectations.
Supporting Evidence:
PMID:17828305
betac via the box 2 motif
GO:0005515 protein binding
IPI
PMID:18692472
The structure of the GM-CSF receptor complex reveals a disti...
MODIFY
Summary: CSF2RB associates with the protein tyrosine kinase JAK2.
Reason: The genuine original 18692472 supplement Figure S5 shows beta-chain immunoprecipitation with JAK2 immunoblotting in human AML mononuclear cells and neutrophils. Refine the partner class to protein tyrosine kinase binding, retaining co-complex assay scope rather than claiming a purified interface or receptor kinase catalysis. PMID:38614096 reports strongest beta association with JAK1 and additional JAK2/TYK2 association in tagged HeLa receptor micropatterning using JAK FERM–SH2 constructs. This assay-specific ranking does not establish a universal native JAK hierarchy or negate the original JAK2 association.
Proposed replacements: protein tyrosine kinase binding
Supporting Evidence:
PMID:38614096
strongest association with JAK1
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005515 protein binding
IPI
PMID:18692472
The structure of the GM-CSF receptor complex reveals a disti...
MODIFY
Summary: CSF2RB contributes GM-CSF contacts in the receptor assembly.
Reason: The original PMID:18692472 supplement supports GM-CSF association with the alpha/beta receptor assembly through purified ectodomain complexes and cellular binding measurements. The ligand identity is GM-CSF (UniProtKB:P04141), distinct from the IL-3 and IL-5 interactions reviewed separately. Cytokine binding was a valid broader description, but a proposed GM-CSF-specific binding term preserves that source specificity. Current GO:0042021 literally describes binding a GM-CSF complex, leaving an unresolved wording/concept distinction from binding the cytokine itself; it is not silently redefined here. The proposed replacement is an ontology request for this existing positive interaction, not a new biological annotation or a claim that beta alone binds free ligand.
Supporting Evidence:
PMID:18692472
human GM-CSF/GM-CSF receptor ternary complex
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005515 protein binding
IPI
PMID:18692472
The structure of the GM-CSF receptor complex reveals a disti...
MODIFY
Summary: The beta-containing IL-3 receptor binds IL-3.
Reason: The genuine 18692472 supplementary binding table and Methods assay IL-3 in cells bearing the appropriate alpha/beta receptor components. Retain positive IL-3 binding at complex-dependent assay scope; do not redescribe it as purified beta-only affinity.
Proposed replacements: interleukin-3 binding
Supporting Evidence:
PMID:8649415
IL-3 could also be coimmunoprecipitated
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005515 protein binding
IPI
PMID:20802515
Inhibition of Ξ²1 integrin and IL-3RΞ² common subunit interact...
MODIFY
Summary: The membrane-proximal CSF2RB extracellular region associates with beta1 integrin.
Reason: PMID:20802515 provides human endothelial-progenitor-cell coimmunoprecipitation and extracellular-domain Fc pull-downs from cell lysates, mapping the interaction to the fourth, membrane-proximal domain. GO:0005178 describes the measured partner class without claiming purified direct binding. Blocking this interaction reduces IL-3-dependent STAT5 signaling and growth/vascular responses without reducing the measured cell adhesion; therefore the cell–matrix adhesion-specific child GO:0098640 is not asserted. Human EPC/HEK293/HUVEC and murine endothelial/in vivo contexts are kept distinct.
Proposed replacements: integrin binding
Supporting Evidence:
PMID:20802515
specifically interacted with Ξ²1 integrin
GO:0005515 protein binding
IPI
PMID:29374162
A dual role for the N-terminal domain of the IL-3 receptor i...
MODIFY
Summary: Human beta-containing receptor experiments support IL-3 binding.
Reason: The 29374162 main Methods/Results assay human alpha/beta receptor assembly, IL-3 binding and beta phosphorylation in cellular systems. Its newly solved binary crystal contains IL-3 and alpha, not beta. The IL-3 binding refinement uses the cellular beta-containing receptor evidence and preserves that distinction.
Proposed replacements: interleukin-3 binding
Supporting Evidence:
PMID:29374162
regulates IL-3 binding and signalling
GO:0005515 protein binding
IPI
PMID:9516124
JAK2 and JAK1 constitutively associate with an interleukin-5...
MODIFY
Summary: CSF2RB associates with the IL-5 receptor alpha chain.
Reason: The complete available abstract of PMID:9516124 explicitly reports anti-receptor immunoprecipitation in human TF-h5Ralpha cells and IL-5-induced recruitment of beta-c to IL5RA. Two exact IntAct records retain that experiment and Figure 1A locators. GO:0005137 captures IL-5 receptor binding; it does not imply that CSF2RB is an IL-5 agonist. Full original Methods were not recovered, so construct details beyond that abstract/database scope are not invented. Independent PMID:1495999 supports the same receptor partnership.
Proposed replacements: interleukin-5 receptor binding
Supporting Evidence:
PMID:9516124
IL-5 stimulation induced the recruitment of betac
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0005886 plasma membrane
IEA
GO_REF:0000117
ACCEPT
Summary: Plasma-membrane localization is directly established although the current ARBA predicate match is unresolved.
Reason: The current ARBA00027801 snapshot outputs plasma membrane but none of its 686 complete condition sets matches the authenticated target feature/taxonomy record. This is a current-rule provenance limitation, not evidence against cell-surface CSF2RB. Reconstitution and surface-labeling studies independently establish its plasma-membrane receptor location. The original electronic assertion and rule identifier remain unchanged.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
ARBA:ARBA00027801 UNRESOLVED
The saved current rule has no target-matching branch; independent receptor experiments support the location.
GO:0005886 plasma membrane
NAS
PMID:1396555
Critical cytoplasmic domains of the common beta subunit of t...
ACCEPT
Summary: Human beta-chain constructs signal at the cell surface.
Reason: The original 1396555 human receptor deletion constructs were expressed and measured on mouse BaF3/CTLL2 cells, including surface binding/expression controls and growth signaling. This directly supports activity of membrane-associated beta receptor constructs; the mouse host is not the insert species.
Supporting Evidence:
PMID:1396555
important for transducing the hGM-CSF-mediated growth signals
GO:0005886 plasma membrane
NAS
PMID:1495999
Molecular basis of the membrane-anchored and two soluble iso...
ACCEPT
Summary: The human beta-containing IL-5 receptor is present at the cell surface.
Reason: The original 1495999 coexpression and cell-surface ligand-crosslinking experiments locate the human beta-containing IL-5 receptor assembly at the cell surface. The paper primarily characterizes alpha isoforms; it does not establish beta product equivalence.
Supporting Evidence:
PMID:1495999
only low-affinity binding
GO:0005886 plasma membrane
NAS
PMID:1702217
Molecular cloning of a second subunit of the receptor for hu...
ACCEPT
Summary: Human beta-chain reconstitution establishes cell-surface GM-CSF binding.
Reason: The authentic five-page 1702217 original reconstitutes cell-surface high-affinity human GM-CSF binding and crosslinks ligand to the beta component in transfected cells. It supports the plasma-membrane assertion without needing an intracellular signaling assay.
Supporting Evidence:
PMID:1702217
formation of a high-affinity receptor for GM-CSF
GO:0005886 plasma membrane
TAS
PMID:7556069
Activating point mutations in the common beta subunit of the...
ACCEPT
Summary: Human beta-chain constructs are detected at the cell surface.
Reason: The original 7556069 Methods and Results explicitly measure cell-surface expression of human beta constructs in mouse hematopoietic cell lines by antibody staining and flow cytometry. Its activating mutants and host-dependent growth do not establish identical wild-type behavior in every cell type.
Supporting Evidence:
PMID:7556069
confer factor independence
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-450031
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The human IL3:IL3RA ligand/receptor assembly recruits the membrane beta-chain/JAK2 complex. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-453104
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target is a membrane-receptor component in the phosphorylated SHC1–GRB2–GAB2 assembly; adaptor binding is assigned to the appropriate molecules. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-453111
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target persists in the membrane complex during SHC–GRB2–SOS1 recruitment; no SOS1 exchange activity is assigned to CSF2RB. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-508247
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target-containing receptor complex places GAB2/p85 recruitment at the membrane; this is not a CSF2RB PI3-kinase catalytic annotation. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5672965
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The catalyst set contains a CSF2RB-bearing membrane complex through SOS1; the RAS exchange reaction is not performed by the receptor beta chain. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5686335
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The modeled CSF2RA:CSF2RB complex is at the plasma membrane in the surfactant-protein binding context; this row asserts location, not a newly inferred uptake mechanism. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5686359
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The source models surface-receptor-associated surfactant uptake; the checked target-containing participant supplies the plasma-membrane location, without assuming that all later vesicles contain the receptor. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5688884
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The source contains disease-associated CSF2RB variants in a surface-receptor context. Their impaired surfactant response does not erase the wild-type receptor location or establish equal behavior of the two official products. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5688899
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The defective component is CSF2RA G174R in a complex containing CSF2RB at the plasma membrane; alpha-chain dysfunction is not transferred to CSF2RB. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879907
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: CSF2RB is a plasma-membrane substrate/scaffold in a receptor-phosphorylation reaction; associated tyrosine kinases perform the catalysis. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879909
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The membrane beta-chain/JAK2 complex participates in STAT5 activation; this localization does not assign STAT5 phosphorylation chemistry to CSF2RB. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879910
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target-containing receptor complex is membrane localized during JAK2 activation; JAK2 is the kinase. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879925
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: Membrane-bound CSF2RB retains the phosphorylated SHC1-containing complex; the reaction does not imply intrinsic receptor kinase activity. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879930
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The source places the receptor/JAK2 complex at the membrane and explicitly discusses uncertainty over direct STAT5 binding to beta-c; only localization is accepted here. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879934
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target phosphoreceptor at the plasma membrane recruits SHC1. The source-specific tyrosine numbering is retained without remapping it to every product. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-879942
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The ligand-bound receptor assembly contains membrane CSF2RB; modeled activation stoichiometry is not treated as a universal native oligomer. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-909738
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The membrane receptor complex binds phosphatases SHP1/SHP2; no phosphatase activity is assigned to CSF2RB. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-912527
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target remains part of the membrane assembly during SHC1-mediated GAB2 phosphorylation, with kinase/adaptor roles separate. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-912757
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The serine-phosphorylated membrane beta chain binds 14-3-3 proteins; the historical site numbering remains source-specific. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-913370
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The human IL5:IL5RA complex recruits the membrane CSF2RB:JAK2 participant. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-913371
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The human GM-CSF:CSF2RA complex recruits membrane CSF2RB. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-913374
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: Phosphorylated SHC1/SHIP recruitment occurs on a membrane beta-chain receptor complex; SHIP enzymatic activity is not transferred to CSF2RB. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-913424
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The stabilized SHC1:SHIP1:GRB2 assembly retains the target membrane receptor component. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-913451
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The beta chain is the membrane substrate for serine phosphorylation, not the serine kinase. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-914036
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: CSF2RB is the membrane phosphoprotein acted on by SHP1/SHP2; no phosphatase function is inferred for it. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-914182
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The 14-3-3/PI3K-recruitment complex contains the surface beta chain; CSF2RB is not a PI3 kinase. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-921155
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The target-containing receptor remains at the membrane while phosphorylated STAT5 dissociates. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005886 plasma membrane
TAS
Reactome:R-NUL-879922
ACCEPT
Summary: The specified Reactome participant contains plasma-membrane CSF2RB.
Reason: The record is explicitly a chimeric model of mouse JAK2 binding human CSF2RB; the human membrane beta-chain participant is verified, and the R-NUL identifier is preserved. The saved original event and a complete witnessed component path end at reference entity UniProtKB:P32927 with plasma-membrane compartment. This validates the location without assigning every activity in the event title to the target.
GO:0005894 interleukin-3 receptor complex
NAS
PMID:29374162
A dual role for the N-terminal domain of the IL-3 receptor i...
ACCEPT
Summary: CSF2RB is a component of the IL-3 receptor complex.
Reason: The 29374162 main cellular experiments and construct Methods support beta participation in the IL-3 receptor complex. Its binary IL-3/alpha crystal must not be described as a beta-containing crystal. Complex membership does not impose a universal native stoichiometry.
Supporting Evidence:
PMID:29374162
cell-surface heterodimer
GO:0005895 interleukin-5 receptor complex
NAS
PMID:1495999
Molecular basis of the membrane-anchored and two soluble iso...
ACCEPT
Summary: CSF2RB is a component of the IL-5 receptor complex.
Reason: The original 1495999 human alpha/beta coexpression and ligand-crosslinking support IL-5 receptor-complex membership. The current GO:0005895 definition contains an internal first-clause IL-3 typo despite its IL-5 label and remaining alpha/beta description; record the ontology anomaly, not a biological denial of this complex.
GO:0007165 signal transduction
NAS
PMID:1702217
Molecular cloning of a second subunit of the receptor for hu...
MODIFY
Summary: The broad signaling assertion is refined to the GM-CSF pathway.
Reason: Refine generic signal transduction to the GM-CSF pathway. The original 1702217 experiment establishes high-affinity receptor assembly, while downstream signaling is corroborated by the separately read 1396555 deletion/response experiments and later studies. Do not claim that the 1990 reconstitution itself measured a positive signaling endpoint.
GO:0007165 signal transduction
NAS
PMID:1833065
A human high affinity interleukin-5 receptor (IL5R) is compo...
MODIFY
Summary: The broad signaling assertion is refined to the source-specific IL-5 pathway.
Reason: PMID1833065 is the human IL-5 alpha/shared-beta receptor paper. Its complete available abstract supports that receptor context, with original full text not recovered here. Refine the broad NAS process using this source context and the independently established IL-5 receptor role; do not confuse it with the adjacent IL-3 publication.
Supporting Evidence:
PMID:1833065
beta chain of the human granulocyte-macrophage
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IBA
GO_REF:0000033
ACCEPT
Summary: CSF2RB is the shared receptor component that couples cytokine binding to JAK–STAT signaling.
Reason: The authentic PTHR23037 v19 tree places the human target below PTN000548082, which carries the exact JAK–STAT IBD. The target itself is legitimate experimental descendant evidence, supported by receptor-mutant and phosphorylation assays in PMID:16437163 and PMID:18692472. No loss record lies on its path. Signal transmission by the receptor is distinct from catalytic phosphorylation by recruited JAKs.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000548082 SUPPORTS TRANSFER
Actual on-path IBD for GO:0007259 is grounded by human P32927 experimental evidence; self-inclusion is expected.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IDA
PMID:18692472
The structure of the GM-CSF receptor complex reveals a disti...
ACCEPT
Summary: CSF2RB participates in receptor-initiated JAK–STAT signaling.
Reason: The actual 18692472 supplement includes JAK2 association, beta receptor phosphorylation and STAT5 assay Methods; the complete main article was not recovered. Retain the curator-supported JAK-STAT pathway, corroborated by the later full 38614096 signaling experiments, without claiming every main-paper panel was inspected.
Supporting Evidence:
PMID:18692472
receptor activation and signaling
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IDA
PMID:9516124
JAK2 and JAK1 constitutively associate with an interleukin-5...
ACCEPT
Summary: Human IL-5 receptor assembly activates JAK/STAT signaling.
Reason: The complete available PMID:9516124 abstract reports IL-5-induced receptor recruitment and JAK1/JAK2, beta-chain and STAT5 phosphorylation in TF-h5Ralpha cells. This positively supports the existing JAK–STAT process at a receptor-participation scope; it does not make CSF2RB a kinase. Full original Methods were unavailable, and no unreported construct or site details are assumed. Independent receptor-mutant signaling data corroborate the process.
GO:0007585 respiratory gaseous exchange by respiratory system
TAS
PMID:9410898
Human pulmonary alveolar proteinosis associated with a defec...
MARK AS OVER ANNOTATED
Summary: Pulmonary receptor dysfunction does not establish a performed gas-exchange step.
Reason: The full 9410898 human clinical study supports a real relationship between deficient beta-chain receptor expression/function and pulmonary alveolar proteinosis. It does not identify CSF2RB as performing gas diffusion, ventilation or another step of the gaseous-exchange process defined by GO:0007585. The proposed route is impaired macrophage surfactant clearance/homeostasis. Preserve that positive physiology and receptor function while treating this direct process attribution as over-extended; do not claim pulmonary effects are absent.
Supporting Evidence:
PMID:9410898
an expression defect of beta c
GO:0008284 positive regulation of cell population proliferation
NAS
PMID:33602937
Interleukin-3 is a predictive marker for severity and outcom...
MODIFY
Summary: CSF2RB signaling promotes leukocyte proliferation; the cited infection study primarily measures recruitment.
Reason: PMID:33602937 examines human disease associations and mouse IL-3/CD131-dependent CXCL12 production and pDC recruitment. Its measured increase in cell numbers is not treated as a direct cell-division assay. Independently, PMID:16437163 measures receptor-dependent BrdU incorporation/colony growth and PMID:18692472 supplies signaling/proliferation evidence. Together these support refinement to GO:0070665, a typed child of the original broad proliferation-regulation term. The original NAS citation remains preserved and its narrower access/endpoint scope is explicit.
Supporting Evidence:
PMID:16437163
as well as proliferation
GO:0009897 external side of plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: The extracellular receptor domains occupy the external side of the plasma membrane.
Reason: PTN000547990 carries the exact external-side IBD and is an ancestor of the authenticated human target. The donor identities and same-term records are traceable, and CSF2RB surface labeling and extracellular ligand-binding experiments independently support this topology. This does not imply that its cytoplasmic signaling region is extracellular.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000547990 SUPPORTS TRANSFER
The exact external-side IBD is on the target path; target receptor topology independently supports the placement.
GO:0015026 coreceptor activity
IDA
PMID:7957082
Three residues in the common beta chain of the human GM-CSF,...
ACCEPT
Summary: CSF2RB performs cooperative coreceptor activity.
Reason: The full 7957082 original uses human beta point mutants with appropriate alpha chains in COS cells and measures ligand-specific high-affinity conversion with surface-expression controls. That performed cooperative ligand-receptor role fits the literal coreceptor definition. It is not intrinsic kinase catalysis.
Supporting Evidence:
PMID:7957082
essential for high affinity ligand-binding and signal transduction
GO:0015026 coreceptor activity
IDA
PMID:8649415
Human interleukin-3 (IL-3) induces disulfide-linked IL-3 rec...
ACCEPT
Summary: IL-3-dependent alpha/beta assembly supports coreceptor activity.
Reason: The complete available 8649415 abstract reports IL-3-dependent human alpha/beta association and loss of activation after blocking disulfide linkage without loss of high-affinity binding. Full main access remained unavailable despite preserved attempts. Retain the clearly established coreceptor function with curator deference rather than reject the IDA from incomplete access.
Supporting Evidence:
PMID:8649415
not high-affinity binding
GO:0016020 membrane
IEA
GO_REF:0000120
ACCEPT
Summary: CSF2RB is an integral membrane cytokine-receptor subunit.
Reason: Both actual InterPro mapping sources and the UniProt membrane-location keyword support the broad electronic membrane annotation. The signal peptide, single transmembrane segment and experimental cell-surface receptor studies agree. A broader electronic term is retained alongside independently supported plasma-membrane annotations without diagnosing a failed transfer.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR003531 SUPPORTS TRANSFER
Actual cytokine-receptor conserved-site mapping includes membrane.
InterPro:IPR011365 SUPPORTS TRANSFER
Actual beta-chain family mapping includes membrane.
UniProtKB-SubCell:SL-0162 SUPPORTS TRANSFER
The supplied membrane-location vocabulary source agrees with target topology.
GO:0016064 immunoglobulin mediated immune response
IBA
GO_REF:0000033
UNDECIDED
Summary: The ancestral immunoglobulin-response assertion is real, but its applicability to CSF2RB remains unresolved.
Reason: The human target is below PTN002745775 and the exact IBD is grounded in mouse Il9r (MGI:96564), not a missing node or a donor-count problem. PMID:30082831 directly demonstrates IL9R-dependent memory-B-cell recall responses using knockout, adoptive-transfer and chimera experiments. That receptor uses IL9R alpha and the common gamma chain. These experiments establish the donor process but do not resolve whether the shared IL-3/IL-5/GM-CSF beta chain performs the broadly defined immunoglobulin-mediated response. No target-specific loss or universal absence of immune participation is asserted.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
PANTHER:PTN002745775 UNRESOLVED
Actual on-path IBD and valid IL9R donor response are preserved; target participation in this broad antibody-response process remains unestablished.
Supporting Evidence:
PMID:30082831
impaired recall antibody responses
GO:0019221 cytokine-mediated signaling pathway
IEA
GO_REF:0000120
ACCEPT
Summary: The beta chain participates in cytokine-mediated signaling.
Reason: ARBA00028236 has two fully evaluated matching current branches: IPR013783/PTHR23037/Primates and the pair of authenticated FunFam matches. IPR011365 independently maps this beta-chain family to cytokine-mediated signaling. Direct receptor reconstitution and signaling assays support the broad biological claim; cytokine-specific routes are represented separately.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
ARBA:ARBA00028236 SUPPORTS TRANSFER
All 60 branches evaluated; target matches branches 0 and 50 with the exact recorded family/feature/taxon predicates.
InterPro:IPR011365 SUPPORTS TRANSFER
Actual beta-chain family mapping outputs GO:0019221 and agrees with receptor experiments.
GO:0030526 granulocyte macrophage colony-stimulating factor receptor complex
IDA
PMID:27396825
Conformational Changes in the GM-CSF Receptor Suggest a Mole...
ACCEPT
Summary: CSF2RB belongs to the GM-CSF receptor complex.
Reason: The actual 27396825 indexed main windows and original supplement support the beta-containing GM-CSF receptor complex through ectodomain purification, a refined ternary structure and cellular functional constructs. No full main PDF was read, and a modeled/crystallographic higher-order assembly is not universal native stoichiometry.
Supporting Evidence:
PMID:27396825
Ξ²c interactions control high-affinity binding
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0030526 granulocyte macrophage colony-stimulating factor receptor complex
TAS
PMID:9410898
Human pulmonary alveolar proteinosis associated with a defec...
ACCEPT
Summary: The clinical receptor study supports GM-CSF receptor-complex membership.
Reason: The full 9410898 clinical paper directly examines human beta-chain expression and GM-CSF binding/response, within established alpha/beta receptor composition. It supports the TAS complex membership without resolving a unique oligomeric arrangement.
GO:0032496 response to lipopolysaccharide
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Rat beta-chain expression increases after LPS exposure.
Reason: The exact rat donor G3V608 and ENSRNOP00000000203 lead to the IEP annotation from PMID:7643220. Its complete available abstract explicitly reports increased receptor mRNA in cultured microglia and rat brain after LPS. GO:0032496 includes stimulus-dependent gene-expression changes, so a separate protective or signaling-output assay is not required for this broad response term. The contextual transfer is retained as non-core with rat species and abstract-only/full-Methods access limits explicit. The IEP record is retained at its expression-pattern evidence scope, not recast as an IMP or direct mechanistic experiment.
Propagation Review
Root cause: NO FAILURE NON CORE
Sources checked:
UniProtKB:G3V608 SUPPORTS TRANSFER
Exact rat donor identity and IEP GO:0032496/PMID:7643220 join; observed microglial/brain expression response, not a human perturbation assay.
ENSEMBL:ENSRNOP00000000203 SUPPORTS TRANSFER
Exact rat donor identity and IEP GO:0032496/PMID:7643220 join; observed microglial/brain expression response, not a human perturbation assay.
Supporting Evidence:
PMID:7643220
marked upregulation of rIL-3R beta mRNA
GO:0036016 cellular response to interleukin-3
IEA
GO_REF:0000108
ACCEPT
Summary: IL-3 binding is transduced by the alpha/beta receptor assembly.
Reason: The actual logical-inference premise is GO:0004912. The original contributes-to receptor activity is supported at complex scope, and IL-3-dependent beta-chain recruitment, phosphorylation and downstream signaling establish a cellular response to IL-3. This is receptor participation rather than a necessity-only or ligand-substrate inference.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
GO:0004912 SUPPORTS TRANSFER
The preserved IL-3 receptor-activity premise is valid at beta-chain contribution scope and agrees with direct IL-3 response experiments.
GO:0038023 signaling receptor activity
TAS
PMID:9410898
Human pulmonary alveolar proteinosis associated with a defec...
MODIFY
Summary: The shared cooperative receptor role is more specifically coreceptor activity.
Reason: The broad signaling-receptor assertion is sound. Coreceptor activity is a signaling-receptor child that more precisely describes the shared beta chain combining with cytokines in cooperation with the private alpha receptor. This is a refinement of the performed cooperative role, not a rejection of receptor activity because the beta chain acts in a complex. It is compatible with the accepted cytokine-receptor assertions. Clinical PMID:9410898 provides receptor dysfunction context; direct assembly, affinity and signaling evidence comes from PMIDs:7957082, 1396555 and 38614096. The beta chain contributes ligand contacts and signal transduction but has no intrinsic kinase activity.
Proposed replacements: coreceptor activity
GO:0038043 interleukin-5-mediated signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: The shared beta chain participates in IL-5-mediated signaling.
Reason: The authentic target path includes PTN000548082 and its exact GO:0038043 IBD, grounded by human P32927 experimental evidence. Self-inclusion of the target is legitimate descendant evidence, not circular propagation. The receptor engages cytokine/alpha-chain assemblies and transmits signals through associated intracellular proteins; the existing direct source PMID:1495999 supports this role. No target-path loss is present.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000548082 SUPPORTS TRANSFER
Actual on-path GO:0038043 IBD with experimental human-target grounding.
GO:0038043 interleukin-5-mediated signaling pathway
IDA
PMID:1495999
Molecular basis of the membrane-anchored and two soluble iso...
ACCEPT
Summary: IL-5 receptor assembly is a signaling-initiation step.
Reason: The original 1495999 experiment establishes the ligand-binding receptor-assembly step of the IL-5 pathway using human components. This is participation in the initiation step, even though that paper does not measure downstream phosphorylation. Subsequent actual 38614096 experiments corroborate signaling through the beta/IL5RA pair.
Supporting Evidence:
PMID:1495999
led to a 2-fold increase
GO:0038043 interleukin-5-mediated signaling pathway
NAS
PMID:7888666
Interleukin-5 signaling in human eosinophils involves JAK2 t...
ACCEPT
Summary: The shared beta chain participates in the established IL-5 pathway.
Reason: The complete 7888666 abstract reports IL-5-induced JAK2 phosphorylation and STAT-containing DNA-binding complexes in primary human eosinophils. Its beta-specific mechanistic details were not independently verified from full text. Retain the NAS pathway in the established shared-receptor context without inventing a beta perturbation experiment.
Supporting Evidence:
PMID:7888666
IL-5 induced rapid and transient tyrosine phosphorylation of JAK2
GO:0038156 interleukin-3-mediated signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: The shared beta chain participates in IL-3-mediated signaling.
Reason: The authentic target path includes PTN000548082 and its exact GO:0038156 IBD, grounded by human P32927 experimental evidence. Self-inclusion of the target is legitimate descendant evidence, not circular propagation. The receptor engages cytokine/alpha-chain assemblies and transmits signals through associated intracellular proteins; the existing direct source PMID:8649415 supports this role. No target-path loss is present.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000548082 SUPPORTS TRANSFER
Actual on-path GO:0038156 IBD with experimental human-target grounding.
GO:0038156 interleukin-3-mediated signaling pathway
IDA
PMID:8649415
Human interleukin-3 (IL-3) induces disulfide-linked IL-3 rec...
ACCEPT
Summary: Ligand-dependent alpha/beta assembly initiates IL-3 signaling.
Reason: The available 8649415 abstract directly links ligand-induced alpha/beta assembly to IL-3 receptor activation. Full Methods/Results remain unavailable in this consultation; preserve the experimentally curated pathway with explicit access limits and independent corroboration, rather than infer a source error.
Supporting Evidence:
PMID:8649415
human IL-3 induces heterodimerization
GO:0038156 interleukin-3-mediated signaling pathway
NAS
PMID:10851052
IL-3 signaling and the role of Src kinases, JAKs and STATs: ...
ACCEPT
Summary: IL-3 signaling is supported at the shared-receptor level.
Reason: PMID10851052 is a review, and only its complete abstract was read. It discusses IL-3/JAK/Src/STAT signaling rather than supplying a new beta-chain experiment. Retain the NAS pathway on the established receptor mechanism while labeling this reference as synthesis.
Supporting Evidence:
PMID:10851052
cell proliferation and cell survival
GO:0038157 granulocyte-macrophage colony-stimulating factor signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: The shared beta chain participates in GM-CSF-mediated signaling.
Reason: The authentic target path includes PTN000548082 and its exact GO:0038157 IBD, grounded by human P32927 experimental evidence. Self-inclusion of the target is legitimate descendant evidence, not circular propagation. The receptor engages cytokine/alpha-chain assemblies and transmits signals through associated intracellular proteins; the existing direct source PMID:18692472 supports this role. No target-path loss is present.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000548082 SUPPORTS TRANSFER
Actual on-path GO:0038157 IBD with experimental human-target grounding.
GO:0038157 granulocyte-macrophage colony-stimulating factor signaling pathway
IDA
PMID:18692472
The structure of the GM-CSF receptor complex reveals a disti...
ACCEPT
Summary: CSF2RB participates in GM-CSF receptor signaling.
Reason: The genuine 18692472 supplement contains human receptor expression, ligand binding, signaling assays and mutant functional experiments. It supports performed participation in GM-CSF receptor signaling. The full main article remains unavailable, and its higher-order model should not become a universal assembly requirement.
Supporting Evidence:
PMID:18692472
receptor activation and signaling
file:human/CSF2RB/CSF2RB-source-evidence.yaml
GO:0070665 positive regulation of leukocyte proliferation
IBA
GO_REF:0000033
ACCEPT
Summary: The shared beta chain participates in positive regulation of leukocyte proliferation.
Reason: The authentic target path includes PTN000548082 and its exact GO:0070665 IBD, grounded by human P32927 experimental evidence. Self-inclusion of the target is legitimate descendant evidence, not circular propagation. The receptor engages cytokine/alpha-chain assemblies and transmits signals through associated intracellular proteins; the existing direct source PMID:18692472 supports this role. No target-path loss is present.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000548082 SUPPORTS TRANSFER
Actual on-path GO:0070665 IBD with experimental human-target grounding.
GO:0070665 positive regulation of leukocyte proliferation
IDA
PMID:18692472
The structure of the GM-CSF receptor complex reveals a disti...
ACCEPT
Summary: Receptor signaling promotes hematopoietic cell proliferation.
Reason: The 18692472 original supplement includes hematopoietic proliferation assays and Figure S6 mutant-versus-wild-type colony formation in receptor-deficient mouse fetal-liver cells reconstituted with receptor components. This is positive receptor-mediated regulation of leukocyte proliferation, with human receptor constructs and mouse cellular context kept distinct.
Supporting Evidence:
PMID:16437163
as well as proliferation
file:human/CSF2RB/CSF2RB-source-evidence.yaml

Core Functions

Cooperates with the ligand-specific alpha chains to assemble signaling receptors for GM-CSF, IL-3 and IL-5, contributing ligand contacts and affinity conversion and coupling receptor engagement to associated JAK signaling at the plasma membrane. The beta chain is not itself a protein kinase; the alpha chains also contribute to productive signaling. In the 2024 tagged-receptor HeLa recruitment assay, beta associated most strongly with JAK1 FERM–SH2 constructs, with additional JAK2 and TYK2 association; this is not a universal native kinase preference.

Supporting Evidence:

References

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Suggested Questions for Experts

Q: Does the six-residue extracellular insertion in P32927-2 change ligand-specific affinity, receptor assembly or signaling when compared under matched expression conditions?

Q: How do receptor assembly distributions vary with ligand, cell type and membrane compartment, given the different structural, live-cell and engineered-receptor assay contexts?

Q: Does CSF2RB itself participate in an immunoglobulin-mediated response corresponding to the broad ancestral IBD, beyond the established IL9R donor program?

Q: Can the first clause of the current GO:0005895 definition be corrected to agree with its IL-5 receptor label and remaining definition?

Q: Should GO:0042021 be clarified to denote binding the GM-CSF cytokine, or should a distinct GM-CSF ligand-binding child of cytokine binding be created? Its current complex-binding wording differs from the corresponding IL-3 and IL-5 ligand-binding definitions.

Suggested Experiments

Experiment: Compare sequence-verified P32927-1 and P32927-2 with each matched alpha chain, controlling surface abundance, ligand affinity, JAK/STAT responses and cell survival/proliferation.

Hypothesis: The extracellular insertion may modify ligand-specific receptor behavior without changing the common membrane/signaling topology.

πŸ“š Additional Documentation

Notes

(CSF2RB-notes.md)

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