Pathway Human Homo sapiens

Signaling by MET

R-HSA-6806834 in Reactome release 97: under Signaling by Receptor Tyrosine Kinases, with 79 genes placed in it by the mapping files and 8 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-6806834 (mouse), R-RNO-6806834 (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-6806834.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-09-19
Last updated: 2021-09-15
Events inside: 8, counted from the record

MET is a receptor tyrosine kinase (RTK) (Cooper et al. 1984, Park et al. 1984) activated by binding to its ligand, Hepatocyte growth factor/Scatter factor (HGF/SF) (Bottaro et al. 1991, Naldini et al. 1991). Similar to other related RTKs, such as EGFR, ligand binding induces MET dimerization and trans-autophosphorylation, resulting in the active MET receptor complex (Ferracini et al. 1991, Longati et al. 1994, Rodrigues and Park 1994, Kirchhofer et al. 2004, Stamos et al. 2004, Hays and Watowich 2004). Phosphorylated tyrosines in the cytoplasmic tail of MET serve as docking sites for binding of adapter proteins, such as GRB2, SHC1 and GAB1, which trigger signal transduction cascades that activate PI3K/AKT, RAS, STAT3, PTK2, RAC1 and RAP1 signaling (Ponzetto et al. 1994, Pelicci et al. 1995, Weidner et al. 1995, Besser et al. 1997, Shen and Novak 1997, Beviglia and Kramer 1999, Rodrigues et al. 2000, Sakkab et al. 2000, Schaeper et al. 2000, Lamorte et al. 2002, Wang et al. 2002, Chen and Chen 2006, Palamidessi et al. 2008, Chen et al. 2011, Murray et al. 2014).

Activation of PLC gamma 1 (PLCG1) signaling by MET remains unclear. It has been reported that PLCG1 can bind to MET directly (Ponzetto et al. 1994) or be recruited by phosphorylated GAB1 (Gual et al. 2000). Tyrosine residue Y307 of GAB1 that serves as docking sites for PLCG1 may be phosphorylated either by activated MET (Watanabe et al. 2006) or SRC (Chan et al. 2010). Another PCLG1 docking site on GAB1, tyrosine residue Y373, was reported as the SRC target, while the kinase for the main PLCG1 docking site, Y407 of GAB1, is not known (Chan et al. 2010).

Signaling by MET promotes cell growth, cell survival and motility, which are essential for embryonic development (Weidner et al. 1993, Schmidt et al. 1995, Uehara et al. 1995, Bladt et al. 1995, Maina et al. 1997, Maina et al. 2001, Helmbacher et al. 2003) and tissue regeneration (Huh et al. 2004, Borowiak et al. 2004, Liu 2004, Chmielowiec et al. 2007). MET signaling is frequently aberrantly activated in cancer, through MET overexpression or activating MET mutations (Schmidt et al. 1997, Pennacchietti et al. 2003, Smolen et al. 2006, Bertotti et al. 2009).

Considerable progress has recently been made in the development of HGF-MET inhibitors in cancer therapy. These include inhibitors of HGF activators, HGF inhibitors and MET antagonists, which are protein therapeutics that act outside the cell. Kinase inhibitors function inside the cell and have constituted the largest effort towards MET-based therapeutics (Gherardi et al. 2012).

Pathogenic bacteria of the species Listeria monocytogenes, exploit MET receptor as an entryway to host cells (Shen et al. 2000, Veiga and Cossart 2005, Neimann et al. 2007).

For review of MET signaling, please refer to Birchmeier et al. 2003, Trusolino et al. 2010, Gherardi et al. 2012, Petrini 2015.

Literature Reactome attaches

A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor familyCell, 1994, vol. 77, p. 261-71PubMed 7513258
Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesisOncogene, 2000, vol. 19, p. 1509-18PubMed 10734310
Differential phosphorylation of the docking protein Gab1 by c-Src and the hepatocyte growth factor receptor regulates different aspects of cell functionsOncogene, 2010, vol. 29, p. 698-710PubMed 19881549
Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinaseJ. Biol. Chem., 1991, vol. 266, p. 19558-64PubMed 1655790
Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET proto-oncogene (HGF receptor)Oncogene, 1994, vol. 9, p. 49-57PubMed 8302603
Autophosphorylation modulates the kinase activity and oncogenic potential of the Met receptor tyrosine kinaseOncogene, 1994, vol. 9, p. 2019-27PubMed 8208547

Reactome's record lists 9 orthologous events, R-RNO-6806834 (Rattus norvegicus), R-MMU-6806834 (Mus musculus) among the species this site serves, and 7 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Signaling by MET". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-6806834 with StableID: R-HSA-6806834.4 (accessed 2026-10-01 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 79 genes in this human pathway; showing 1 to 79, 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
GeneARF6	AuthorityHGNC:659	Mapping file id382 NCBI file	EvidenceTAS
GeneCBL	AuthorityHGNC:1541	Mapping file id867 NCBI file	EvidenceTAS
GeneCOL11A1	AuthorityHGNC:2186	Mapping file id1301 NCBI file	EvidenceTAS
GeneCOL11A2	AuthorityHGNC:2187	Mapping file id1302 NCBI file	EvidenceTAS
GeneCOL1A1	AuthorityHGNC:2197	Mapping file id1277 NCBI file	EvidenceTAS
GeneCOL1A2	AuthorityHGNC:2198	Mapping file id1278 NCBI file	EvidenceTAS
GeneCOL24A1	AuthorityHGNC:20821	Mapping file id255631 NCBI file	EvidenceTAS
GeneCOL27A1	AuthorityHGNC:22986	Mapping file id85301 NCBI file	EvidenceTAS
GeneCOL2A1	AuthorityHGNC:2200	Mapping file id1280 NCBI file	EvidenceTAS
GeneCOL3A1	AuthorityHGNC:2201	Mapping file id1281 NCBI file	EvidenceTAS
GeneCOL5A1	AuthorityHGNC:2209	Mapping file id1289 NCBI file	EvidenceTAS
GeneCOL5A2	AuthorityHGNC:2210	Mapping file id1290 NCBI file	EvidenceTAS
GeneCOL5A3	AuthorityHGNC:14864	Mapping file id50509 NCBI file	EvidenceTAS
GeneCRK	AuthorityHGNC:2362	Mapping file id1398 NCBI file	EvidenceTAS
GeneCRKL	AuthorityHGNC:2363	Mapping file id1399 NCBI file	EvidenceTAS
GeneDOCK7	AuthorityHGNC:19190	Mapping file id85440 NCBI file	EvidenceTAS
GeneEPS15	AuthorityHGNC:3419	Mapping file id2060 NCBI file	EvidenceTAS
GeneFN1	AuthorityHGNC:3778	Mapping file id2335 NCBI file	EvidenceTAS
GeneGAB1	AuthorityHGNC:4066	Mapping file id2549 NCBI file	EvidenceTAS
GeneGGA3	AuthorityHGNC:17079	Mapping file id23163 NCBI file	EvidenceTAS
GeneGRB2	AuthorityHGNC:4566	Mapping file id2885 NCBI file	EvidenceTAS
GeneHGF	AuthorityHGNC:4893	Mapping file id3082 NCBI file	EvidenceTAS
GeneHGFAC	AuthorityHGNC:4894	Mapping file id3083 NCBI file	EvidenceTAS
GeneHGS	AuthorityHGNC:4897	Mapping file id9146 NCBI file	EvidenceTAS
GeneHPN	AuthorityHGNC:5155	Mapping file id3249 NCBI file	EvidenceTAS
GeneHRAS	AuthorityHGNC:5173	Mapping file id3265 NCBI file	EvidenceTAS
GeneITGA2	AuthorityHGNC:6137	Mapping file id3673 NCBI file	EvidenceTAS
GeneITGA3	AuthorityHGNC:6139	Mapping file id3675 NCBI file	EvidenceTAS
GeneITGB1	AuthorityHGNC:6153	Mapping file id3688 NCBI file	EvidenceTAS
GeneKRAS	AuthorityHGNC:6407	Mapping file id3845 NCBI file	EvidenceTAS
GeneLAMA1	AuthorityHGNC:6481	Mapping file id284217 NCBI file	EvidenceTAS
GeneLAMA2	AuthorityHGNC:6482	Mapping file id3908 NCBI file	EvidenceTAS
GeneLAMA3	AuthorityHGNC:6483	Mapping file id3909 NCBI file	EvidenceTAS
GeneLAMA4	AuthorityHGNC:6484	Mapping file id3910 NCBI file	EvidenceTAS
GeneLAMA5	AuthorityHGNC:6485	Mapping file id3911 NCBI file	EvidenceTAS
GeneLAMB1	AuthorityHGNC:6486	Mapping file id3912 NCBI file	EvidenceTAS
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
GeneLRIG1	AuthorityHGNC:17360	Mapping file id26018 NCBI file	EvidenceTAS
GeneMET	AuthorityHGNC:7029	Mapping file id4233 NCBI file	EvidenceTAS
GeneMUC20	AuthorityHGNC:23282	Mapping file id200958 NCBI file	EvidenceTAS
GeneNRAS	AuthorityHGNC:7989	Mapping file id4893 NCBI file	EvidenceTAS
GenePIK3CA	AuthorityHGNC:8975	Mapping file id5290 NCBI file	EvidenceTAS
GenePIK3R1	AuthorityHGNC:8979	Mapping file id5295 NCBI file	EvidenceTAS
GenePTK2	AuthorityHGNC:9611	Mapping file id5747 NCBI file	EvidenceTAS
GenePTPN1	AuthorityHGNC:9642	Mapping file id5770 NCBI file	EvidenceTAS
GenePTPN11	AuthorityHGNC:9644	Mapping file id5781 NCBI file	EvidenceTAS
GenePTPN2	AuthorityHGNC:9650	Mapping file id5771 NCBI file	EvidenceTAS
GenePTPRJ	AuthorityHGNC:9673	Mapping file id5795 NCBI file	EvidenceTAS
GeneRAB4A	AuthorityHGNC:9781	Mapping file id5867 NCBI file	EvidenceTAS
GeneRAB4B	AuthorityHGNC:9782	Mapping file id53916 NCBI file	EvidenceTAS
GeneRAC1	AuthorityHGNC:9801	Mapping file id5879 NCBI file	EvidenceTAS
GeneRANBP10	AuthorityHGNC:29285	Mapping file id57610 NCBI file	EvidenceTAS
GeneRANBP9	AuthorityHGNC:13727	Mapping file id10048 NCBI file	EvidenceTAS
GeneRAP1A	AuthorityHGNC:9855	Mapping file id5906 NCBI file	EvidenceTAS
GeneRAP1B	AuthorityHGNC:9857	Mapping file id5908 NCBI file	EvidenceTAS
GeneRAPGEF1	AuthorityHGNC:4568	Mapping file id2889 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneSH3GL1	AuthorityHGNC:10830	Mapping file id6455 NCBI file	EvidenceTAS
GeneSH3GL2	AuthorityHGNC:10831	Mapping file id6456 NCBI file	EvidenceTAS
GeneSH3GL3	AuthorityHGNC:10832	Mapping file id6457 NCBI file	EvidenceTAS
GeneSH3KBP1	AuthorityHGNC:13867	Mapping file id30011 NCBI file	EvidenceTAS
GeneSHC1	AuthorityHGNC:10840	Mapping file id6464 NCBI file	EvidenceTAS
GeneSOS1	AuthorityHGNC:11187	Mapping file id6654 NCBI file	EvidenceTAS
GeneSPINT1	AuthorityHGNC:11246	Mapping file id6692 NCBI file	EvidenceTAS
GeneSPINT2	AuthorityHGNC:11247	Mapping file id10653 NCBI file	EvidenceTAS
GeneSRC	AuthorityHGNC:11283	Mapping file id6714 NCBI file	EvidenceTAS
GeneSTAM	AuthorityHGNC:11357	Mapping file id8027 NCBI file	EvidenceTAS
GeneSTAM2	AuthorityHGNC:11358	Mapping file id10254 NCBI file	EvidenceTAS
GeneSTAT3	AuthorityHGNC:11364	Mapping file id6774 NCBI file	EvidenceIEA, TAS
GeneTNS3	AuthorityHGNC:21616	Mapping file id64759 NCBI file	EvidenceTAS
GeneTNS4	AuthorityHGNC:24352	Mapping file id84951 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
GeneUSP8	AuthorityHGNC:12631	Mapping file id9101 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 Receptor Tyrosine KinasesR-HSA-9006934536 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.