BioPAX pathway converted from "MET activates PI3K/AKT signaling" in the Reactome database.

MET activates PI3K/AKT signaling

This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>

Activated MET binds GAB1

Reactome DB_ID: 9771359

plasma membraneGO0005886HGF:p-Y1234,Y1235,Y1349,Y1356-MET dimer [plasma membrane]

HGF:p-Y1234,Y1235,Y1349,Y1356-MET dimer

Reactome DB_ID: 9771357

HGF dimer:p-Y1234,Y1235,Y1349,Y1356-MET [plasma membrane]

HGF dimer:p-Y1234,Y1235,Y1349,Y1356-MET

Reactome DB_ID: 9744781

extracellular regionGO0005576HGF dimer [extracellular region]

HGF dimer

Reactome DB_ID: 9744779

UniProt:Q08048 Hgf

Hgf

HgfFUNCTION Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.SUBUNIT Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts with SRPX2; the interaction increases HGF mitogenic activity.SIMILARITY Belongs to the peptidase S1 family. Plasminogen subfamily.CAUTION Has lost two of the three essential catalytic residues and so probably has no enzymatic activity.

Reactomehttp://www.reactome.orgMus musculus

NCBI Taxonomy10090UniProtQ08048

Chain Coordinates

EQUAL

494

EQUAL

Reactome DB_ID: 9744777

495

EQUAL

728

EQUAL

Reactome Database ID Release 759744781Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9744781ReactomeR-MMU-141763

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-141763.1

Reactome DB_ID: 9771355

UniProt:P16056Met

UniProtP16056

O4'-phospho-L-tyrosine at 1234 (in Homo sapiens)

1234

EQUAL

O4'-phospho-L-tyrosine [MOD:00048]

O4'-phospho-L-tyrosine at 1235 (in Homo sapiens)

1235

EQUAL

O4'-phospho-L-tyrosine at 1349 (in Homo sapiens)

1349

EQUAL

O4'-phospho-L-tyrosine at 1356 (in Homo sapiens)

1356

EQUAL

1390

EQUAL

Reactome Database ID Release 759771357Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9771357ReactomeR-MMU-6806975

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6806975.1Reactome Database ID Release 759771359Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9771359ReactomeR-MMU-6806977

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6806977.1

Reactome DB_ID: 9713986

cytosolGO0005829

UniProt:Q9QYY0 Gab1

Gab1

Gab1FUNCTION Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. Plays a role in FGFR1 signaling. Probably involved in signaling by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Involved in the MET/HGF-signaling pathway.SUBUNIT Interacts with GRB2 and with other SH2-containing proteins (PubMed:11353842). Interacts with phosphorylated LAT2. Interacts with PTPRJ (By similarity). Interacts (phosphorylated) with PTPN11 (By similarity). Interacts with HCK (By similarity). Identified in a complex containing FRS2, GRB2, GAB1, PIK3R1 and SOS1 (By similarity). Part of a tripartite complex containing GAB1, METTL13 and SPRY2. Interacts with METTL13 (By similarity).TISSUE SPECIFICITY Expressed in the inner ear. Expression is detected in the cochlear duct, spiral limbus region, efferent and afferent nerves, and in spiral ganglion neurons.PTM Phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine phosphorylation of GAB1 mediates interaction with several proteins that contain SH2 domains. Phosphorylated on tyrosine residues by HCK upon IL6 signaling (By similarity). Phosphorylated in response to FGFR1 activation.SIMILARITY Belongs to the GAB family.

UniProtQ9QYY0

EQUAL

694

EQUAL

Reactome DB_ID: 9803892

HGF:p-4Y-MET dimer:GAB1 [plasma membrane]

HGF:p-4Y-MET dimer:GAB1

Reactome DB_ID: 9771359

Reactome DB_ID: 9713986

EQUAL

694

EQUAL

Reactome Database ID Release 759803892Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803892ReactomeR-MMU-8851913

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851913.1Reactome Database ID Release 759803894Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803894ReactomeR-MMU-8851908

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851908.1The adapter protein GAB1 can directly bind to phosphorylated MET receptor via its MET binding domain (MBD) (Schaeper et al. 2000, Lock et al. 2003).

10871282Pubmed2000Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responsesSchaeper, UGehring, N HFuchs, K PSachs, MKempkes, BBirchmeier, WJ. Cell Biol. 149:1419-3212766170Pubmed2003Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domainLock, LSFrigault, MMSaucier, CPark, MJ Biol Chem 278:30083-90inferred by electronic annotationIEAGOIEA

Activated MET binds GAB1 and GRB2

Reactome DB_ID: 9712289

UniProt:Q60631 Grb2

Grb2

Grb2FUNCTION Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.FUNCTION Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced. transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death (By similarity).SUBUNIT Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (By similarity). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (PubMed:8943348). Interacts with IRS4 (when Tyr-phosphorylated) (PubMed:11113178). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains (By similarity). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (By similarity). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (By similarity). Interacts with phosphorylated MET (By similarity). Interacts with phosphorylated TOM1L1 (PubMed:11711534). Interacts with the phosphorylated C-terminus of SH2B2 (By similarity). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:16249387, PubMed:14610044, PubMed:15477350, PubMed:15477348, PubMed:22561606). Interacts with NISCH, PTPNS1 and REPS2 (By similarity). Interacts with syntrophin SNTA1 (PubMed:11551227). Interacts (via SH3 domains) with REPS1 (PubMed:9395447). Interacts (via SH3 domains) with PIK3C2B (By similarity). Interacts with CBL and CBLB (By similarity). Interacts with AJUBA and CLNK (PubMed:10330178, PubMed:11463797). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (PubMed:10521483). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (By similarity). Interacts with PTPN11 (PubMed:8943348). Interacts with PRNP (PubMed:11571277). Interacts with RALGPS1 (By similarity). Interacts also with HCST (PubMed:16582911). Interacts with KDR (PubMed:16966330). Interacts with FLT1 (tyrosine-phosphorylated) (PubMed:9722576). Interacts with GAPT and PTPRE (By similarity). Interacts (via SH2 domain) with KIF26A (By similarity). Interacts (via SH3 2) with GAB2 (PubMed:10068651). Interacts with ADAM15 (By similarity). Interacts with THEMIS2 (PubMed:20644716). Interacts (via SH2 domain) with AXL (phosphorylated) (By similarity). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:10377264). Interacts with PTPRJ and BCR (By similarity). Interacts with PTPN23 (By similarity). Interacts with FLT4 (tyrosine phosphorylated) (By similarity). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:12925710). Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with ERBB4 (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:7997267). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (By similarity). Interacts (via SH2-domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-58' (PubMed:21930792, PubMed:28098138, PubMed:28290451). Interacts (via SH3 domains) with GAREM1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (By similarity). Interacts with DAB2 (PubMed:9569023). Interacts with TESPA1 (By similarity). Interacts with THEMIS (PubMed:19597498, PubMed:19597497, PubMed:19805304, PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (PubMed:22561606). Interacts with CD28 (By similarity). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (PubMed:21543326). Interacts with ASAP3 (phosphorylated form) (By similarity). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064). Interacts with PTPRO (phosphorylated form) (PubMed:20398064). Interacts with PTPRB (phosphorylated form) (PubMed:20398064). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (By similarity). Interacts with DENND2B (By similarity). Interacts (via SH3 domain) with ZDHHC19 (via SH3-binding motif); leading to recruit STAT3 (By similarity).TISSUE SPECIFICITY Expressed in macrophages.DOMAIN The SH3 domains mediate interaction with RALGPS1 and SHB.SIMILARITY Belongs to the GRB2/sem-5/DRK family.

UniProtQ60631

EQUAL

217

EQUAL

Reactome DB_ID: 9771359

Reactome DB_ID: 9713986

EQUAL

694

EQUAL

Reactome DB_ID: 9803896

HGF:p-4Y-MET dimer:GRB2-1:GAB1 [plasma membrane]

HGF:p-4Y-MET dimer:GRB2-1:GAB1

Reactome DB_ID: 9712289

EQUAL

217

EQUAL

Reactome DB_ID: 9771359

Reactome DB_ID: 9713986

EQUAL

694

EQUAL

Reactome Database ID Release 759803896Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803896ReactomeR-MMU-8851921

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851921.1Reactome Database ID Release 759803898Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803898ReactomeR-MMU-8851919

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851919.1While GAB1 can bind activated MET receptor directly, the presence of GRB2 results in a more stable association between GAB1 and MET (Weidner et al. 1996, Schaeper et al. 2000, Lock et al. 2003).

8906793Pubmed1996Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesisWeidner, K MDi Cesare, SSachs, MBrinkmann, VBehrens, JBirchmeier, WNature 384:173-6inferred by electronic annotationIEAGOIEA

2.7.10

MET phosphorylates GAB1

Converted from EntitySet in Reactome

Reactome DB_ID: 9803913

HGF:p-4Y-MET dimer:GAB1,HGF:p-4Y-MET dimer:GRB2:GAB1 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity

Reactome DB_ID: 113592

ATP(4-) [ChEBI:30616]

ATP(4-)

Adenosine 5'-triphosphateatpATP

ChEBI30616

Reactome DB_ID: 29370

ADP(3-) [ChEBI:456216]

ADP(3-)

ADP trianion5'-O-[(phosphonatooxy)phosphinato]adenosineADP

ChEBI456216Converted from EntitySet in Reactome

Reactome DB_ID: 9771365

HGF:p-4Y-MET:p-5Y-GAB1, HGF:p-4Y-MET:GRB2-1:p-5Y-GAB1 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Converted from EntitySet in Reactome

Reactome DB_ID: 9803913

GO0004713

GO molecular function

Reactome Database ID Release 759803914Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803914Reactome Database ID Release 759803916Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803916ReactomeR-MMU-8851933

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851933.1Activated MET phosphorylates GAB1 on at least five tyrosine residues: Y447, Y472, Y589, Y627 and Y659 (Schaeper et al. 2000, Chan et al. 2010).

19881549Pubmed2010Differential phosphorylation of the docking protein Gab1 by c-Src and the hepatocyte growth factor receptor regulates different aspects of cell functionsChan, P-CSudhakar, J NLai, C-CChen, H-COncogene 29:698-710inferred by electronic annotationIEAGOIEA

Phosphorylated GAB1 recruits PI3K to MET

Converted from EntitySet in Reactome

Reactome DB_ID: 9771365

Reactome DB_ID: 9722464

PIK3CA:PIK3R1 [cytosol]

PIK3CA:PIK3R1

Reactome DB_ID: 9027214

UniProt:P42337 Pik3ca

Pik3ca

Pik3caFUNCTION Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis (PubMed:19604150).SUBUNIT Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:8139567). Interacts with IRS1 in nuclear extracts (PubMed:15197263). Interacts with RUFY3. Interacts with RASD2. Interacts with APPL1 (By similarity). Interacts with HRAS and KRAS (PubMed:17540175). Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (PubMed:17540175). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity).DOMAIN The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1.DISRUPTION PHENOTYPE Lethal. Embryonic fibroblasts cells are resistant to oncogenic transformation induced by oncogenic receptor tyrosine kinases (RTKs), are unable to differentiate into adipocytes and deficient in cellular signaling in response to various growth factors. Defective responsiveness to insulin led to reduced somatic growth, hyperinsulinemia, glucose intolerance, hyperphagia and increased adiposity.SIMILARITY Belongs to the PI3/PI4-kinase family.

UniProtP42337

EQUAL

1068

EQUAL

Reactome DB_ID: 9712301

UniProt:P26450 Pik3r1

Pik3r1

Pik3r1FUNCTION Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348926).SUBUNIT Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2 domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the interaction enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (By similarity). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner (PubMed:20348926). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH and RUFY3 (By similarity). Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR or BCR activation. Interacts with CBLB. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with SOCS7 and HCST. Interacts with AXL, FASLG, FGR, HCK, KIT and BCR. Interacts with PTK2/FAK1 (By similarity). Interacts with PDGFRB (tyrosine phosphorylated) (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with FER. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) (Probable). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with ERBB4. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with APPL1 and APPL2 (PubMed:25328665). Interacts with SRC (By similarity). Interacts with ALOX5; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (By similarity).DOMAIN The SH3 domain mediates the binding to CBLB.PTM Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.PTM Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Dephosphorylated by PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR (By similarity). Phosphorylated by CSF1R. Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by TEK/TIE2.SIMILARITY Belongs to the PI3K p85 subunit family.

UniProtP26450

EQUAL

724

EQUAL

Reactome Database ID Release 759722464Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9722464ReactomeR-MMU-1806218

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1806218.1

Reactome DB_ID: 9771367

HGF:p-4Y-MET:p-5Y-GAB1, HGF:p-4Y-MET:GRB2-1:p-5Y-GAB1:PI3K [plasma membrane]

HGF:p-4Y-MET:p-5Y-GAB1, HGF:p-4Y-MET:GRB2-1:p-5Y-GAB1:PI3K

Converted from EntitySet in Reactome

Reactome DB_ID: 9771365

Reactome DB_ID: 9722464

Reactome Database ID Release 759771367Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9771367ReactomeR-MMU-8851953

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851953.1Reactome Database ID Release 759803918Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803918ReactomeR-MMU-8851954

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851954.1Phosphorylated tyrosine residues Y447, Y472 and Y589 of GAB1 are docking sites for the regulatory subunit PIK3R1 of the phosphatidyl inositol-3 kinase (PI3K) complex (Rodrigues et al. 2000). GAB1, phosphorylated by MET, thus recruits PI3K to activated MET (Schaeper et al. 2000).

10648629Pubmed2000A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signalingRodrigues, GAFalasca, MZhang, ZOng, SHSchlessinger, JMol Cell Biol 20:1448-59inferred by electronic annotationIEAGOIEA

2.7.1.153

MET bound PI3K generates PIP3

Reactome DB_ID: 113592

Reactome DB_ID: 179856

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [ChEBI:18348]

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate

PIP2

ChEBI18348

Reactome DB_ID: 29370

Reactome DB_ID: 179838

1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate [ChEBI:16618]

1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate

PIP3

ChEBI16618PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9771367

GO0046934

GO molecular function

Reactome Database ID Release 759803941Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803941Reactome Database ID Release 759803943Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9803943ReactomeR-MMU-8852019

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8852019.1Phosphatidylinositol-4,5-bisphosphate 3-kinase, PI3K, recruited to activated receptor tyrosine kinases such as EGFR (Rodrigues et al. 2000) and MET (Schaeper et al. 2000) via GAB1, catalyzes phosphatidylinositol-3,4,5-triphosphate (PIP3) synthesis, triggering downstream signaling by AKT family kinases.

inferred by electronic annotationIEAGOIEA

Reactome Database ID Release 759820292Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9820292ReactomeR-MMU-8851907

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8851907.1MET binds and phosphorylates the adapter protein GAB1, thus creating a docking site for the regulatory subunit PIK3R1 of the PI3K complex. Recruitment of PI3K to MET-bound phosphorylated GAB1 results in PI3K activation, production of PIP3, and stimulation of downstream AKT signaling (Rodrigues et al. 2000, Schaeper et al. 2000).

inferred by electronic annotationIEAGOIEA