Pathway Human Homo sapiens

Signal Transduction

R-HSA-162582 in Reactome release 97: a top-level pathway, with 2,631 genes placed in it by the mapping files and 17 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-162582 (mouse), R-RNO-162582 (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-162582.13
Class: TopLevelPathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2011-09-20
Last updated: 2023-06-07
Events inside: 17, counted from the record
Also named: Signaling Pathways

Signal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such as hormones and growth factors, or reacting to other types of stimuli, such as light. Stimulation of transmembrane receptors leads to their conformational change which propagates the signal to the intracellular environment by activating downstream signaling cascades. Depending on the cellular context, this may impact cellular proliferation, differentiation, and survival. On the organism level, signal transduction regulates overall growth and behavior.

Receptor tyrosine kinases (RTKs) transmit extracellular signals by phosphorylating their protein partners on conserved tyrosine residues. Some of the best studied RTKs are EGFR (reviewed in Avraham and Yarden, 2011), FGFR (reviewed in Eswarakumar et al, 2005), insulin receptor (reviewed in Saltiel and Kahn, 2001), NGF (reviewed in Reichardt, 2006), PDGF (reviewed in Andrae et al, 2008) and VEGF (reviewed in Xie et al, 2004). RTKs frequently activate downstream signaling through RAF/MAP kinases (reviewed in McKay and Morrison, 2007 and Wellbrock et al 2004), AKT (reviewed in Manning and Cantley, 2007) and PLC- gamma (reviewed in Patterson et al, 2005), which ultimately results in changes in gene expression and cellular metabolism.

Receptor serine/threonine kinases of the TGF-beta family, such as TGF-beta receptors (reviewed in Kang et al. 2009) and BMP receptors (reviewed in Miyazono et al. 2009), transmit extracellular signals by phosphorylating regulatory SMAD proteins on conserved serine and threonine residues. This leads to formation of complexes of regulatory SMADs and SMAD4, which translocate to the nucleus where they act as transcription factors.

WNT receptors transmit their signal through beta-catenin. In the absence of ligand, beta-catenin is constitutively degraded in a ubiquitin-dependent manner. WNT receptor stimulation releases beta-catenin from the destruction complex, allowing it to translocate to the nucleus where it acts as a transcriptional regulator (reviewed in MacDonald et al, 2009 and Angers and Moon, 2009). WNT receptors were originally classified as G-protein coupled receptors (GPCRs). Although they are structurally related, GPCRs primarily transmit their signals through G-proteins, which are trimers of alpha, beta and gamma subunits. When a GPCR is activated, it acts as a guanine nucleotide exchange factor, catalyzing GDP to GTP exchange on the G-alpha subunit of the G protein and its dissociation from the gamma-beta heterodimer. The G-alpha subunit regulates the activity of adenylate cyclase, while the gamma-beta heterodimer can activate AKT and PLC signaling (reviewed in Rosenbaum et al. 2009, Oldham and Hamm 2008, Ritter and Hall 2009).

NOTCH receptors are activated by transmembrane ligands expressed on neighboring cells, which results in cleavage of NOTCH receptor and release of its intracellular domain. NOTCH intracellular domain translocates to the nucleus where it acts as a transcription factor (reviewed in Kopan and Ilagan, 2009).

Integrins are activated by extracellular matrix components, such as fibronectin and collagen, leading to conformational change and clustering of integrins on the cell surface. This results in activation of integrin-linked kinase and other cytosolic kinases and, in co-operation with RTK signaling, regulates survival, proliferation and cell shape and adhesion (reviewed in Hehlgans et al, 2007) .

Besides inducing changes in gene expression and cellular metabolism, extracellular signals that trigger the activation of Rho GTP-ases can trigger changes in the organization of cytoskeleton, thereby regulating cell polarity and cell-cell junctions (reviewed in Citi et al, 2011).

Literature Reactome attaches

AKT/PKB signaling: navigating downstreamCell, 2007, vol. 129, p. 1261-74PubMed 17604717
The canonical Notch signaling pathway: unfolding the activation mechanismCell, 2009, vol. 137, p. 216-33PubMed 19379690
New regulatory mechanisms of TGF-beta receptor functionTrends Cell Biol, 2009, vol. 19, p. 385-94PubMed 19648010
Bone morphogenetic protein receptors and signal transductionJ Biochem, 2010, vol. 147, p. 35-51PubMed 19762341
Feedback regulation of EGFR signalling: decision making by early and delayed loopsNat Rev Mol Cell Biol, 2011, vol. 12, p. 104-17PubMed 21252999
Heterotrimeric G protein activation by G-protein-coupled receptorsNat Rev Mol Cell Biol, 2008, vol. 9, p. 60-71PubMed 18043707
Fine-tuning of GPCR activity by receptor-interacting proteinsNat Rev Mol Cell Biol, 2009, vol. 10, p. 819-30PubMed 19935667

Reactome's record lists 14 orthologous events, R-MMU-162582 (Mus musculus), R-RNO-162582 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-06 ET · Reactome pathway browser"Signal Transduction". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-162582 with StableID: R-HSA-162582.13 (accessed 2026-10-06 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 2,631 genes in this human pathway; showing 1,301 to 1,400, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 14 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneLAMB2	AuthorityHGNC:6487	Mapping file id3913 NCBI file	EvidenceTAS
GeneLAMB3	AuthorityHGNC:6490	Mapping file id3914 NCBI file	EvidenceTAS
GeneLAMC1	AuthorityHGNC:6492	Mapping file id3915 NCBI file	EvidenceTAS
GeneLAMC2	AuthorityHGNC:6493	Mapping file id3918 NCBI file	EvidenceTAS
GeneLAMC3	AuthorityHGNC:6494	Mapping file id10319 NCBI file	EvidenceTAS
GeneLAMTOR1	AuthorityHGNC:26068	Mapping file id55004 NCBI file	EvidenceTAS
GeneLAMTOR2	AuthorityHGNC:29796	Mapping file id28956 NCBI file	EvidenceTAS
GeneLAMTOR3	AuthorityHGNC:15606	Mapping file id8649 NCBI file	EvidenceTAS
GeneLAMTOR4	AuthorityHGNC:33772	Mapping file id389541 NCBI file	EvidenceTAS
GeneLAMTOR5	AuthorityHGNC:17955	Mapping file id10542 NCBI file	EvidenceTAS
GeneLAT	AuthorityHGNC:18874	Mapping file id27040 NCBI file	EvidenceTAS
GeneLATS1	AuthorityHGNC:6514	Mapping file id9113 NCBI file	EvidenceTAS
GeneLATS2	AuthorityHGNC:6515	Mapping file id26524 NCBI file	EvidenceTAS
GeneLBR	AuthorityHGNC:6518	Mapping file id3930 NCBI file	EvidenceTAS
GeneLCK	AuthorityHGNC:6524	Mapping file id3932 NCBI file	EvidenceIEA, TAS
GeneLEF1	AuthorityHGNC:6551	Mapping file id51176 NCBI file	EvidenceIEA, TAS
GeneLEMD3	AuthorityHGNC:28887	Mapping file id23592 NCBI file	EvidenceTAS
GeneLEO1	AuthorityHGNC:30401	Mapping file id123169 NCBI file	EvidenceTAS
GeneLEP	AuthorityHGNC:6553	Mapping file id3952 NCBI file	EvidenceIEA
GeneLEPR	AuthorityHGNC:6554	Mapping file id3953 NCBI file	EvidenceIEA
GeneLETM1	AuthorityHGNC:6556	Mapping file id3954 NCBI file	EvidenceTAS
GeneLFNG	AuthorityHGNC:6560	Mapping file id3955 NCBI file	EvidenceIEA
GeneLGR4	AuthorityHGNC:13299	Mapping file id55366 NCBI file	EvidenceTAS
GeneLGR5	AuthorityHGNC:4504	Mapping file id8549 NCBI file	EvidenceTAS
GeneLGR6	AuthorityHGNC:19719	Mapping file id59352 NCBI file	EvidenceTAS
GeneLHB	AuthorityHGNC:6584	Mapping file id3972 NCBI file	EvidenceTAS
GeneLHCGR	AuthorityHGNC:6585	Mapping file id3973 NCBI file	EvidenceTAS
GeneLIMK1	AuthorityHGNC:6613	Mapping file id3984 NCBI file	EvidenceIEA, TAS
GeneLIMK2	AuthorityHGNC:6614	Mapping file id3985 NCBI file	EvidenceIEA
GeneLIN7B	AuthorityHGNC:17788	Mapping file id64130 NCBI file	EvidenceTAS
GeneLINGO1	AuthorityHGNC:21205	Mapping file id84894 NCBI file	EvidenceTAS
GeneLMAN1	AuthorityHGNC:6631	Mapping file id3998 NCBI file	EvidenceTAS
GeneLMNB1	AuthorityHGNC:6637	Mapping file id4001 NCBI file	EvidenceTAS
GeneLPAR1	AuthorityHGNC:3166	Mapping file id1902 NCBI file	EvidenceTAS
GeneLPAR2	AuthorityHGNC:3168	Mapping file id9170 NCBI file	EvidenceTAS
GeneLPAR3	AuthorityHGNC:14298	Mapping file id23566 NCBI file	EvidenceTAS
GeneLPAR4	AuthorityHGNC:4478	Mapping file id2846 NCBI file	EvidenceTAS
GeneLPAR5	AuthorityHGNC:13307	Mapping file id57121 NCBI file	EvidenceTAS
GeneLPAR6	AuthorityHGNC:15520	Mapping file id10161 NCBI file	EvidenceTAS
GeneLRIG1	AuthorityHGNC:17360	Mapping file id26018 NCBI file	EvidenceTAS
GeneLRP5	AuthorityHGNC:6697	Mapping file id4041 NCBI file	EvidenceIEA, TAS
GeneLRP6	AuthorityHGNC:6698	Mapping file id4040 NCBI file	EvidenceIEA, TAS
GeneLRRC1	AuthorityHGNC:14307	Mapping file id55227 NCBI file	EvidenceTAS
GeneLRRC41	AuthorityHGNC:16917	Mapping file id10489 NCBI file	EvidenceTAS
GeneLRRC7	AuthorityHGNC:18531	Mapping file id57554 NCBI file	EvidenceTAS
GeneLRRK2	AuthorityHGNC:18618	Mapping file id120892 NCBI file	EvidenceTAS
GeneLTB4R	AuthorityHGNC:6713	Mapping file id1241 NCBI file	EvidenceTAS
GeneLTB4R2	AuthorityHGNC:19260	Mapping file id56413 NCBI file	EvidenceTAS
GeneLTBP1	AuthorityHGNC:6714	Mapping file id4052 NCBI file	EvidenceTAS
GeneLTBP2	AuthorityHGNC:6715	Mapping file id4053 NCBI file	EvidenceTAS
GeneLTBP3	AuthorityHGNC:6716	Mapping file id4054 NCBI file	EvidenceTAS
GeneLTBP4	AuthorityHGNC:6717	Mapping file id8425 NCBI file	EvidenceTAS
GeneLTK	AuthorityHGNC:6721	Mapping file id4058 NCBI file	EvidenceTAS
GeneLYL1	AuthorityHGNC:6734	Mapping file id4066 NCBI file	EvidenceTAS
GeneLYN	AuthorityHGNC:6735	Mapping file id4067 NCBI file	EvidenceIEA, TAS
GeneLYPLA1	AuthorityHGNC:6737	Mapping file id10434 NCBI file	EvidenceTAS
GeneMACO1	AuthorityHGNC:25572	Mapping file id55219 NCBI file	EvidenceTAS
GeneMAD1L1	AuthorityHGNC:6762	Mapping file id8379 NCBI file	EvidenceTAS
GeneMAD2L1	AuthorityHGNC:6763	Mapping file id4085 NCBI file	EvidenceTAS
GeneMADD	AuthorityHGNC:6766	Mapping file id8567 NCBI file	EvidenceTAS
GeneMAF1	AuthorityHGNC:24966	Mapping file id84232 NCBI file	EvidenceIEA, TAS
GeneMAG	AuthorityHGNC:6783	Mapping file id4099 NCBI file	EvidenceTAS
GeneMAGED1	AuthorityHGNC:6813	Mapping file id9500 NCBI file	EvidenceIEA
GeneMAML1	AuthorityHGNC:13632	Mapping file id9794 NCBI file	EvidenceIEA, TAS
GeneMAML2	AuthorityHGNC:16259	Mapping file id84441 NCBI file	EvidenceIEA, TAS
GeneMAML3	AuthorityHGNC:16272	Mapping file id55534 NCBI file	EvidenceIEA, TAS
GeneMAMLD1	AuthorityHGNC:2568	Mapping file id10046 NCBI file	EvidenceIEA, TAS
GeneMAP2K1	AuthorityHGNC:6840	Mapping file id5604 NCBI file	EvidenceTAS
GeneMAP2K2	AuthorityHGNC:6842	Mapping file id5605 NCBI file	EvidenceTAS
GeneMAP2K5	AuthorityHGNC:6845	Mapping file id5607 NCBI file	EvidenceIEA
GeneMAP3K11	AuthorityHGNC:6850	Mapping file id4296 NCBI file	EvidenceTAS
GeneMAP3K7	AuthorityHGNC:6859	Mapping file id6885 NCBI file	EvidenceTAS
GeneMAPK1	AuthorityHGNC:6871	Mapping file id5594 NCBI file	EvidenceIEA, TAS
GeneMAPK11	AuthorityHGNC:6873	Mapping file id5600 NCBI file	EvidenceIEA, TAS
GeneMAPK12	AuthorityHGNC:6874	Mapping file id6300 NCBI file	EvidenceIEA, TAS
GeneMAPK13	AuthorityHGNC:6875	Mapping file id5603 NCBI file	EvidenceIEA, TAS
GeneMAPK14	AuthorityHGNC:6876	Mapping file id1432 NCBI file	EvidenceIEA, TAS
GeneMAPK3	AuthorityHGNC:6877	Mapping file id5595 NCBI file	EvidenceIEA, TAS
GeneMAPK4	AuthorityHGNC:6878	Mapping file id5596 NCBI file	EvidenceTAS
GeneMAPK6	AuthorityHGNC:6879	Mapping file id5597 NCBI file	EvidenceTAS
GeneMAPK7	AuthorityHGNC:6880	Mapping file id5598 NCBI file	EvidenceIEA, TAS
GeneMAPK8	AuthorityHGNC:6881	Mapping file id5599 NCBI file	EvidenceIEA, TAS
GeneMAPKAP1	AuthorityHGNC:18752	Mapping file id79109 NCBI file	EvidenceTAS
GeneMAPKAPK2	AuthorityHGNC:6887	Mapping file id9261 NCBI file	EvidenceTAS
GeneMAPKAPK3	AuthorityHGNC:6888	Mapping file id7867 NCBI file	EvidenceTAS
GeneMAPKAPK5	AuthorityHGNC:6889	Mapping file id8550 NCBI file	EvidenceTAS
GeneMAPRE1	AuthorityHGNC:6890	Mapping file id22919 NCBI file	EvidenceTAS
GeneMARK3	AuthorityHGNC:6897	Mapping file id4140 NCBI file	EvidenceTAS
GeneMAS1	AuthorityHGNC:6899	Mapping file id4142 NCBI file	EvidenceIEA
GeneMATK	AuthorityHGNC:6906	Mapping file id4145 NCBI file	EvidenceTAS
GeneMBD3	AuthorityHGNC:6918	Mapping file id53615 NCBI file	EvidenceIEA, TAS
GeneMC1R	AuthorityHGNC:6929	Mapping file id4157 NCBI file	EvidenceTAS
GeneMC2R	AuthorityHGNC:6930	Mapping file id4158 NCBI file	EvidenceTAS
GeneMC3R	AuthorityHGNC:6931	Mapping file id4159 NCBI file	EvidenceTAS
GeneMC4R	AuthorityHGNC:6932	Mapping file id4160 NCBI file	EvidenceTAS
GeneMC5R	AuthorityHGNC:6933	Mapping file id4161 NCBI file	EvidenceTAS
GeneMCAM	AuthorityHGNC:6934	Mapping file id4162 NCBI file	EvidenceTAS
GeneMCF2	AuthorityHGNC:6940	Mapping file id4168 NCBI file	EvidenceTAS
GeneMCF2L	AuthorityHGNC:14576	Mapping file id23263 NCBI file	EvidenceTAS
GeneMCHR1	AuthorityHGNC:4479	Mapping file id2847 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

None: this is a top-level pathway of the release.

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.