Pathway Human Homo sapiens

Interleukin-3, Interleukin-5 and GM-CSF signaling

R-HSA-512988 in Reactome release 97: under Signaling by Interleukins, with 48 genes placed in it by the mapping files and 2 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-512988 (mouse), R-RNO-512988 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-512988.8
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2010-09-21
Last updated: 2018-09-30
Events inside: 27, counted from the record

The Interleukin-3 (IL-3), IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) receptors form a family of heterodimeric receptors that have specific alpha chains but share a common beta subunit, often referred to as the common beta (Bc). Both subunits contain extracellular conserved motifs typical of the cytokine receptor superfamily. The cytoplasmic domains have limited similarity with other cytokine receptors and lack detectable catalytic domains such as tyrosine kinase domains.

IL-3 is a 20-26 kDa product of CD4+ T cells that acts on the most immature marrow progenitors. IL-3 is capable of inducing the growth and differentiation of multi-potential hematopoietic stem cells, neutrophils, eosinophils, megakaryocytes, macrophages, lymphoid and erythroid cells. IL-3 has been used to support the proliferation of murine cell lines with properties of multi-potential progenitors, immature myeloid as well as T and pre-B lymphoid cells (Miyajima et al. 1992). IL-5 is a hematopoietic growth factor responsible for the maturation and differentiation of eosinophils. It was originally defined as a T-cell-derived cytokine that triggers activated B cells for terminal differentiation into antibody-secreting plasma cells. It also promotes the generation of cytotoxic T-cells from thymocytes. IL-5 induces the expression of IL-2 receptors (Kouro & Takatsu 2009). GM-CSF is produced by cells (T-lymphocytes, tissue macrophages, endothelial cells, mast cells) found at sites of inflammatory responses. It stimulates the growth and development of progenitors of granulocytes and macrophages, and the production and maturation of dendritic cells. It stimulates myeloblast and monoblast differentiation, synergises with Epo in the proliferation of erythroid and megakaryocytic progenitor cells, acts as an autocrine mediator of growth for some types of acute myeloid leukemia, is a strong chemoattractant for neutrophils and eosinophils. It enhances the activity of neutrophils and macrophages. Under steady-state conditions GM-CSF is not essential for the production of myeloid cells, but it is required for the proper development of alveolar macrophages, otherwise, pulmonary alvelolar proteinosis (PAP) develops. A growing body of evidence suggests that GM-CSF plays a key role in emergency hematopoiesis (predominantly myelopoiesis) in response to infection, including the production of granulocytes and macrophages in the bone marrow and their maintenance, survival, and functional activation at sites of injury or insult (Hercus et al. 2009).

All three receptors have alpha chains that bind their specific ligands with low affinity (de Groot et al. 1998). Bc then associates with the alpha chain forming a high affinity receptor (Geijsen et al. 2001), though the in vivo receptor is likely be a higher order multimer as recently demonstrated for the GM-CSF receptor (Hansen et al. 2008).

The receptor chains lack intrinsic kinase activity, instead they interact with and activate signaling kinases, notably Janus Kinase 2 (JAK2). These phosphorylate the common beta subunit, allowing recruitment of signaling molecules such as Shc, the phosphatidylinositol 3-kinases (PI3Ks), and the Signal Transducers and Activators of Transcription (STATs). The cytoplasmic domain of Bc has two distinct functional domains: the membrane proximal region mediates the induction of proliferation-associated genes such as c-myc, pim-1 and oncostatin M. This region binds multiple signal-transducing proteins including JAK2 (Quelle et al. 1994), STATs, c-Src and PI3 kinase (Rao and Mufson, 1995). The membrane distal domain is required for cytokine-induced growth inhibition and is necessary for the viability of hematopoietic cells (Inhorn et al. 1995). This region interacts with signal-transducing proteins such as Shc (Inhorn et al. 1995) and SHP and mediates the transcriptional activation of c-fos, c-jun, c-Raf and p70S6K (Reddy et al. 2000).

Figure reproduced by permission from Macmillan Publishers Ltd: Leukemia, WL Blalock et al. 13:1109-1166, copyright 1999. Note that residue numbering in this diagram refers to the mature Common beta chain with signal peptide removed.

Literature Reactome attaches

Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptorsStem Cells, 1998, vol. 16, p. 301-13PubMed 9766809
Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugsLeukemia, 1999, vol. 13, p. 1109-66PubMed 10450743

Reactome's record lists 10 orthologous events, R-MMU-512988 (Mus musculus), R-RNO-512988 (Rattus norvegicus) among the species this site serves, and 8 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Interleukin-3, Interleukin-5 and GM-CSF signaling". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-512988 with StableID: R-HSA-512988.8 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 48 genes in this human pathway; showing 1 to 48, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneBLNK	AuthorityHGNC:14211	Mapping file id29760 NCBI file	EvidenceIEA
GeneCBL	AuthorityHGNC:1541	Mapping file id867 NCBI file	EvidenceIEA, TAS
GeneCRK	AuthorityHGNC:2362	Mapping file id1398 NCBI file	EvidenceTAS
GeneCRKL	AuthorityHGNC:2363	Mapping file id1399 NCBI file	EvidenceTAS
GeneCSF2	AuthorityHGNC:2434	Mapping file id1437 NCBI file	EvidenceTAS
GeneCSF2RA	AuthorityHGNC:2435	Mapping file id1438 NCBI file	EvidenceTAS
GeneCSF2RB	AuthorityHGNC:2436	Mapping file id1439 NCBI file	EvidenceIEA, TAS
GeneFYN	AuthorityHGNC:4037	Mapping file id2534 NCBI file	EvidenceIEA, TAS
GeneGAB2	AuthorityHGNC:14458	Mapping file id9846 NCBI file	EvidenceTAS
GeneGRB2	AuthorityHGNC:4566	Mapping file id2885 NCBI file	EvidenceIEA, TAS
GeneHCK	AuthorityHGNC:4840	Mapping file id3055 NCBI file	EvidenceIEA, TAS
GeneIL2	AuthorityHGNC:6001	Mapping file id3558 NCBI file	EvidenceTAS
GeneIL2RA	AuthorityHGNC:6008	Mapping file id3559 NCBI file	EvidenceTAS
GeneIL2RB	AuthorityHGNC:6009	Mapping file id3560 NCBI file	EvidenceTAS
GeneIL2RG	AuthorityHGNC:6010	Mapping file id3561 NCBI file	EvidenceTAS
GeneIL3	AuthorityHGNC:6011	Mapping file id3562 NCBI file	EvidenceTAS
GeneIL3RA	AuthorityHGNC:6012	Mapping file id3563 NCBI file	EvidenceTAS
GeneIL5	AuthorityHGNC:6016	Mapping file id3567 NCBI file	EvidenceTAS
GeneIL5RA	AuthorityHGNC:6017	Mapping file id3568 NCBI file	EvidenceTAS
GeneINPP5D	AuthorityHGNC:6079	Mapping file id3635 NCBI file	EvidenceTAS
GeneINPPL1	AuthorityHGNC:6080	Mapping file id3636 NCBI file	EvidenceTAS
GeneJAK1	AuthorityHGNC:6190	Mapping file id3716 NCBI file	EvidenceTAS
GeneJAK2	AuthorityHGNC:6192	Mapping file id3717 NCBI file	EvidenceIEA, TAS
GeneJAK3	AuthorityHGNC:6193	Mapping file id3718 NCBI file	EvidenceTAS
GeneLYN	AuthorityHGNC:6735	Mapping file id4067 NCBI file	EvidenceIEA, TAS
GenePIK3CA	AuthorityHGNC:8975	Mapping file id5290 NCBI file	EvidenceIEA, TAS
GenePIK3CB	AuthorityHGNC:8976	Mapping file id5291 NCBI file	EvidenceIEA, TAS
GenePIK3CD	AuthorityHGNC:8977	Mapping file id5293 NCBI file	EvidenceIEA, TAS
GenePIK3R1	AuthorityHGNC:8979	Mapping file id5295 NCBI file	EvidenceIEA, TAS
GenePIK3R2	AuthorityHGNC:8980	Mapping file id5296 NCBI file	EvidenceIEA, TAS
GenePIK3R3	AuthorityHGNC:8981	Mapping file id8503 NCBI file	EvidenceIEA, TAS
GenePRKACA	AuthorityHGNC:9380	Mapping file id5566 NCBI file	EvidenceTAS
GenePTPN11	AuthorityHGNC:9644	Mapping file id5781 NCBI file	EvidenceIEA, TAS
GenePTPN6	AuthorityHGNC:9658	Mapping file id5777 NCBI file	EvidenceTAS
GeneRAPGEF1	AuthorityHGNC:4568	Mapping file id2889 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneSHC1	AuthorityHGNC:10840	Mapping file id6464 NCBI file	EvidenceTAS
GeneSOS1	AuthorityHGNC:11187	Mapping file id6654 NCBI file	EvidenceTAS
GeneSTAT5A	AuthorityHGNC:11366	Mapping file id6776 NCBI file	EvidenceIEA, TAS
GeneSTAT5B	AuthorityHGNC:11367	Mapping file id6777 NCBI file	EvidenceIEA, TAS
GeneSYK	AuthorityHGNC:11491	Mapping file id6850 NCBI file	EvidenceIEA, TAS
GeneTEC	AuthorityHGNC:11719	Mapping file id7006 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneVAV1	AuthorityHGNC:12657	Mapping file id7409 NCBI file	EvidenceTAS
GeneYES1	AuthorityHGNC:12841	Mapping file id7525 NCBI file	EvidenceIEA, TAS
GeneYWHAZ	AuthorityHGNC:12855	Mapping file id7534 NCBI file	EvidenceTAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Signaling by InterleukinsR-HSA-449147465 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.