CSF2RA

Summary: Human alpha receptor specifically binds GM-CSF in the original PMID:2555171 expression/cloning experiments.

Reason: Human alpha receptor specifically binds GM-CSF in the original PMID:2555171 expression/cloning experiments. Together with common beta it forms the high-affinity signaling receptor demonstrated in PMID:1702217 and the 2016 binding/mutagenesis studies. The specific GM-CSF receptor MF refines cytokine receptor activity; this is receptor participation, not intrinsic kinase activity. The authored core represents this cooperative activity with contributes_to_molecular_function while retaining direct cytokine binding as the subunit molecular function; the literal source qualifier is preserved.

Proposed replacements: granulocyte macrophage colony-stimulating factor receptor activity

Summary: The GHR-specific activity does not match the demonstrated ligand specificity of CSF2RA.

Reason: The authentic PTHR23036 v19 tree contains the exact CSF2RA sequence below PTN002745520, and the captured current IBD for growth hormone receptor activity is genuinely on that path. Its extant GHR experimental support is real. Human CSF2RA instead recognizes GM-CSF and assembles with common beta, as directly demonstrated by PMID:2555171, PMID:1702217 and PMID:27396825. This is a ligand-specific propagation error across diverged receptor functions, not a missing-node or donor-count objection. GM-CSF receptor activity is represented by the refinements of the existing broad receptor annotations.

Summary: A positive human CSF2RA–FATE1 pair is retained at the demonstrated generic-binding scope.

Reason: PMID:25416956 is linked to three positive IntAct records for CSF2RA and FATE1: prey-pooling, array, and validated two-hybrid formats in yeast. All 42 literal fields and both participant sequence identifiers were checked. The experiment supports the pair, but does not establish a native receptor-regulatory mechanism or a more specific molecular activity. The project instruction retains supported generic binding as non-core. The original paper validates subsets by orthogonal assays; those subset results are not asserted for this pair.

Summary: Retain extracellular localization at soluble-product scope, distinct from the surface-exposed ectodomain of membrane isoform1.

Reason: The official SL-0243 mapping explicitly concerns soluble isoforms 3/4/6, not merely the extracellular ectodomain of the membrane receptor. In PMID:1832774, human soluble-receptor cDNA expressed in mouse psi-AM and 32Dcl3 cells produced conditioned-medium GM-CSF binding with little surface binding; the original Figure 1 terminal sequence matches official isoform 3. This supports a distinct soluble-product location. The activities of isoforms 4/6 and antagonism by the soluble form remain unproved here, so the broad gene-level location is retained as non-core without adding an isoform field to the original assertion.

Summary: Whether CSF2RA performs an activity in the cytosol remains unresolved.

Reason: PTN002745520 genuinely carries the current cytosol IBD and lies on the exact CSF2RA path. The literal is_active_in assertion concerns a site of activity; detecting an intracellular receptor pool would not alone establish it. Human alpha-chain ligand binding and receptor assembly support activity at the extracellular plasma-membrane interface. The identified donor O46600 is bovine GHR; the verified abstract of PMID:16174355 reports membrane and cytoplasm localization, without distinguishing cytosol from intracellular membranes or demonstrating CSF2RA activity there. Its full text was not recovered, but access to donor experiments would still leave the target-specific inference to assess. Unlike the rejected growth-hormone-specific functions, different ligand recognition does not itself demonstrate loss of an ancestral compartment of activity. Retain UNDECIDED because the available evidence neither establishes nor contradicts activity of a defined CSF2RA product in cytosol; this is not an assertion that every intracellular pool is active or that an on-path IBA is invalid merely because direct target data are unavailable.

Summary: The combined automated plasma-membrane assertion is biologically supported, with distinct current provenance for its two sources.

Reason: The current official SL-0039 location is cell membrane and agrees with human receptor binding and surface-expression experiments. The independently evaluated current ARBA00027801 has 686 condition sets and no definite match against the captured official features; nearest branch 15 lacks IPR052672. That version-dependent rule discrepancy is recorded rather than used to reject the plasma-membrane location, which is directly supported by SL-0039 and primary evidence. This gene-level location does not place every secreted splice product in the membrane.

Summary: Original PMID:1702217 measures cell-associated ligand binding, dissociation and crosslinking after human alpha/beta expression in COS7 and NIH3T3, with TF1 comparison.

Reason: Original PMID:1702217 measures cell-associated ligand binding, dissociation and crosslinking after human alpha/beta expression in COS7 and NIH3T3, with TF1 comparison. This supports plasma-membrane receptor localization. Cytoplasmic deletions in that paper concern beta, not alpha.

Summary: Original PMID:2555171 cloned human placental alpha cDNA and measured radioiodinated human GM-CSF binding in intact COS transfectants, including vector controls, competition and receptor crosslinking.

Reason: Original PMID:2555171 cloned human placental alpha cDNA and measured radioiodinated human GM-CSF binding in intact COS transfectants, including vector controls, competition and receptor crosslinking. This directly supports membrane localization for the full-length receptor. It is not a secretion assay of the soluble splice variants.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-453104 concerns SHC1–GRB2–GAB2 recruitment. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-453111 concerns SHC1–GRB2–SOS1 recruitment. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-508247 concerns GAB2 association with the PI3K p85 subunit. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-5672965 concerns RAS nucleotide exchange by receptor-associated GEF machinery. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-5686335 concerns the modeled surfactant-protein uptake reaction. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA. The event model is distinguished from the human PAP papers: those establish receptor defects and abnormal GM-CSF responses, not purified direct CSF2RA–surfactant binding. The G174R paper reports abnormal glycosylation/lower apparent mass, so the cached event wording about truncation is not adopted as a primary result.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-5686359 concerns the modeled surfactant transport reaction. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA. The event model is distinguished from the human PAP papers: those establish receptor defects and abnormal GM-CSF responses, not purified direct CSF2RA–surfactant binding. The G174R paper reports abnormal glycosylation/lower apparent mass, so the cached event wording about truncation is not adopted as a primary result.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-5688884 concerns the disease reaction containing defective CSF2RB. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA. The event model is distinguished from the human PAP papers: those establish receptor defects and abnormal GM-CSF responses, not purified direct CSF2RA–surfactant binding. The G174R paper reports abnormal glycosylation/lower apparent mass, so the cached event wording about truncation is not adopted as a primary result.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-5688899 concerns the disease reaction containing CSF2RA G174R. Its actual entity graph contains CSF2RA G174R, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA. The event model is distinguished from the human PAP papers: those establish receptor defects and abnormal GM-CSF responses, not purified direct CSF2RA–surfactant binding. The G174R paper reports abnormal glycosylation/lower apparent mass, so the cached event wording about truncation is not adopted as a primary result.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879907 concerns receptor-associated tyrosine phosphorylation. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879909 concerns JAK2-dependent STAT5 activation. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879910 concerns JAK2 activation. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879925 concerns phosphorylation of receptor-bound SHC1. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879930 concerns STAT5 recruitment. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879934 concerns SHC1 recruitment at the common beta chain. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-879942 concerns ligand-dependent receptor assembly. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-909738 concerns SHP1/SHP2 association with the common beta chain. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-912527 concerns GAB2 phosphorylation downstream of SHC1. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-912757 concerns 14-3-3 association with the phosphorylated common beta chain. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-913360 concerns direct GM-CSF binding by its alpha receptor. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-913371 concerns association of the alpha–GM-CSF complex with the common beta chain. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-913374 concerns SHIP recruitment by phosphorylated SHC1. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-913424 concerns stabilization of the SHC1–SHIP1–GRB2 complex. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-913451 concerns common-beta-chain Ser585 phosphorylation. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-914036 concerns SHP-dependent common-beta-chain dephosphorylation. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-914182 concerns PI3K recruitment through 14-3-3. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: CSF2RA is a plasma-membrane component in this specific Reactome event.

Reason: R-HSA-921155 concerns STAT5 release from the receptor complex. Its actual entity graph contains CSF2RA, linked to UniProt P15509, at the plasma membrane through the recorded component/member path. This supports the location in the original TAS assertion; the activities of associated kinases, phosphatases, adaptors or GEFs are not assigned to CSF2RA.

Summary: Preserve the experimentally curated JAK-STAT participation of the ligand-recognizing receptor subunit.

Reason: Preserve the experimentally curated JAK-STAT participation of the ligand-recognizing receptor subunit. Actual PMID:18692472 supplementary Methods assay beta/JAK2/STAT5 phosphorylation after GM-CSF in receptor-transduced cells, and FigureS5 tests JAK2 association in human AML cells and neutrophils. JAK2 associates with beta rather than alpha in that assay; this does not negate alpha-mediated receptor activation. Main Results were not recovered, so no new claim of a personally read main STAT5 figure is made. Independent PMID:27396825 alpha-mutant binding/proliferation experiments corroborate a performed signaling role.

Summary: Refine broad positive proliferation to leukocyte proliferation at the target-specific GM-CSF receptor scope.

Reason: Refine broad positive proliferation to leukocyte proliferation at the target-specific GM-CSF receptor scope. The PMID:18692472 supplement measures GM-CSF-dependent colony production using receptor-transduced mouse beta-null/betaIL3-null fetal liver cells and retains control cytokine-cocktail responses; PMID:27396825 measures receptor-mutant proliferation with thymidine incorporation and a human TF1 ligand-mutant assay. This biological precision judgment does not challenge the ancestral placement on donor-count grounds or treat target self-evidence as circular. The specific replacement is already retained from IDA evidence in this review; refinement of this source does not propose an additional annotation.

Proposed replacements: positive regulation of leukocyte proliferation

Summary: The external-side definition explicitly includes embedded or attached membrane proteins.

Reason: The external-side definition explicitly includes embedded or attached membrane proteins. The full-length alpha chain is a single-pass plasma-membrane receptor with a ligand-binding extracellular domain, supported by human-sequence expression/cell-surface binding and soluble-domain structure. No qualifier reinterpretation or inference that the entire polypeptide lies outside the cell is needed.

Summary: Plasma membrane is a directly recorded is_a child of membrane and is supported by the original intact-cell receptor studies.

Reason: Plasma membrane is a directly recorded is_a child of membrane and is supported by the original intact-cell receptor studies. This is a target-specific refinement of a true broad electronic localization, not a conclusion that the source domain mapping is biologically false. Soluble products are separately scoped. Plasma-membrane annotations already retained from other sources supply the same target location; this refinement does not propose an additional annotation.

Proposed replacements: plasma membrane

Summary: Use cytokine binding for the demonstrated GM-CSF ligand interaction.

Reason: The literal IBA links PTN002745520 and GHR donors to peptide hormone binding. The current target path is authentic, but the captured current IBD snapshot lacks an exact GO:0017046 record at that node; no historical loss is inferred from this difference. Direct human GM-CSF binding establishes cytokine binding. This is a source-specific alternative ligand-class description, not an is_a refinement of peptide hormone binding or a categorical claim that cytokines cannot have hormonal effects. The closest current cytokine-binding child, GO:0042021, explicitly names binding to a GM-CSF complex and is not silently equated with binding plain GM-CSF. Cytokine binding is already retained from the separate PTN002745476 inference. MODIFY records reconciliation of this source assertion to the supported target ligand class, not a NEW or second biological function. REMOVE would overstate the evidence against peptide-hormone binding: different GHR specificity does not establish that the broader ligand class is false for GM-CSF.

Proposed replacements: cytokine binding

Summary: GM-CSF-mediated signaling is the supported specific cytokine pathway and is an actual is_a child of GO:0019221.

Reason: GM-CSF-mediated signaling is the supported specific cytokine pathway and is an actual is_a child of GO:0019221. Human alpha ligand recognition, assembly with beta and alpha-mutant functional effects identify the target pathway rather than merely demonstrating generic necessity. This refinement preserves the valid broad biological premise and does not replace the original IBA source object.

Proposed replacements: granulocyte-macrophage colony-stimulating factor signaling pathway

Summary: Retain the true conservative electronic cytokine-signaling assertion; its more specific GM-CSF pathway is represented by existing experimental row44 and the row39 refinement.

Reason: Current ARBA00028236 branch 0 matches all three captured official conditions: IPR013783, PTHR23037 and Primates 9443. The broad cytokine-signaling consequence is biologically correct for the ligand-recognizing GM-CSF receptor subunit. Retain this conservative electronic assertion; the more precise GM-CSF pathway is separately supported by the existing experimental assertion. The v19 PANTHER API family difference is recorded, not silently substituted into this rule.

Summary: Retain direct cytokine binding.

Reason: Retain direct cytokine binding. All 35 current direct is_a child definitions were independently inspected. GO:0042021 explicitly names binding to a GM-CSF complex, not plain GM-CSF ligand, and cannot be silently substituted for the experimentally demonstrated alpha/ligand interaction. GO:0051916 is G-CSF binding, not GM-CSF. The integrated receptor activity GO:0004901 supplies specific functional synthesis without inventing a plain GM-CSF-binding term.

Summary: Human alpha is an experimentally supported component of the GM-CSF receptor complex.

Reason: Human alpha is an experimentally supported component of the GM-CSF receptor complex. PMID:27396825 includes purified engineered soluble alpha/GM-CSF binary complex, revised ternary structural interpretation, and full-length receptor binding/mutagenesis assays. Its complete ternary-alpha model splices binary and ternary coordinates because only part of alpha was well resolved. The existing complex term does not license a fixed native dodecameric stoichiometry or equivalent assembly for all official isoforms.

Summary: The GM-CSF receptor MF is more precise than generic signaling receptor activity and is supported independently by PMID:2555171 / PMID:1702217 / PMID:27396825.

Reason: The GM-CSF receptor MF is more precise than generic signaling receptor activity and is supported independently by PMID:2555171 / PMID:1702217 / PMID:27396825. The original PMID:1358805 source remains unchanged: its complete available abstract describes genomic localization/mapping, and its full text was not assessed. Do not claim that abstract directly assays receptor function or call it miscited solely on this access boundary; the positive biological refinement is a holistic judgment supported by the other originals.

Proposed replacements: granulocyte macrophage colony-stimulating factor receptor activity

Summary: Retain the specific GM-CSF pathway.

Reason: Retain the specific GM-CSF pathway. Ligand binding and receptor assembly are steps performed by alpha; the common beta and associated JAK supply downstream transduction. PMID:18692472 actual supplement documents relevant signaling assays and GM-CSF-dependent colony outcomes, while PMID:27396825 provides alpha-specific mutant functional effects. This does not establish an intrinsic alpha kinase or universal signaling by soluble variants.

Summary: Positive JAK-STAT regulation is biologically consistent with ligand-recognizing alpha promoting productive GM-CSF receptor signaling, independently of whether the propagated ancestral GHR evidence is the best source.

Reason: The authentic current positive JAK-STAT-regulation IBD at PTN002745520 is on the CSF2RA path and has rat GHR experimental support. Unlike the growth-hormone-specific assertions, this shared process is also supported by human CSF2RA: primary myeloid cells and alpha/beta-transfected 293 cells with the G174R alpha chain have reduced GM-CSF-dependent STAT5 responses, with partial rescue at higher ligand concentration (PMID:18955570). The 2008 supplement documents assembled-receptor JAK2/STAT5 assays. Alpha-mediated ligand recognition/assembly promotes signaling; kinase catalysis belongs to associated JAK proteins.

Summary: The growth-hormone-specific pathway does not describe the established CSF2RA receptor mechanism.

Reason: The on-path PTN002745520 current IBD and GHR donor experiments are authentic. GO:0060396 specifically follows physiological ligand binding by the growth hormone receptor. Human CSF2RA directly recognizes GM-CSF and recruits common beta into its cytokine receptor complex; generic shared downstream signaling does not make this a growth-hormone receptor pathway. The existing experimental GM-CSF signaling assertion and broad-pathway refinement retain the positive target biology.

Summary: The homomeric growth-hormone receptor complex is not the demonstrated GM-CSF receptor complex.

Reason: GO:0070195 explicitly consists of two identical subunits binding growth hormone. Its current IBD is genuinely placed at on-path PTN002745520 and has human GHR experimental support. CSF2RA forms the ligand-specific alpha component of the alpha/common-beta GM-CSF receptor, as shown by the original reconstitution and structural/functional studies. Shared receptor-family architecture does not support this ligand-specific homomeric complex; the existing GO:0030526 annotation preserves the correct complex membership.

Summary: Retain positive leukocyte proliferation in the GM-CSF-responsive hematopoietic context.

Reason: Retain positive leukocyte proliferation in the GM-CSF-responsive hematopoietic context. The original PMID:18692472 supplementary fetal-liver colony experiment and PMID:27396825 receptor-transduced proliferation assays support the receptor activity leading to this outcome. This is neither generalized proliferation in every tissue nor independent catalytic growth stimulation by the alpha chain alone.