BioPAX pathway converted from "Activated FGFR3:p-FRS:p-PTPN11 activates RAS nucleotide exchange" in the Reactome database.Activated FGFR3:p-FRS:p-PTPN11 activates RAS nucleotide exchangeActivated FGFR3:p-FRS:p-PTPN11 activates RAS nucleotide exchangeRAS nucleotide is stimulated downstream of activated FGFR3 in a p-PTPN11-dependent manner. The phosphatase activity of PTPN11 is required for activation of the RAS-MAP kinase pathway, although the mechanism for RAS pathway activation is not yet clear (Hadari et al, 1998; reviewed in Mohi et al, 2007; Gotoh et al, 2008).Authored: Rothfels, K, 2011-08-15Reviewed: Gotoh, N, 2011-08-26Edited: Rothfels, Karen, 2016-10-05Reactome DB_ID: 294381cytosolGO0005829GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateReactomehttp://www.reactome.orgChEBI15996Reactome DB_ID: 1097961plasma membraneGO0005886p21 RAS:GDP [plasma membrane]p21 RAS:GDPReactome DB_ID: 294201GDP [ChEBI:17552]GDPGuanosine 5'-diphosphateGuanosine diphosphateChEBI17552Converted from EntitySet in ReactomeReactome DB_ID: 96497151mature p21 RAS [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityS-Farn-Me PalmS NRAS [plasma membrane]S-Farn-Me KRAS4B [plasma membrane]S-Farn-Me-PalmS KRAS4A [plasma membrane]S-Farn-Me-2xPalmS HRAS [plasma membrane]UniProtP01111UniProtP01116-2UniProtP01116-1UniProtP01112Homo sapiensNCBI Taxonomy9606Reactome Database ID Release 71109796Database 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=109796ReactomeR-HSA-1097962Reactome 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-HSA-109796.2Reactome DB_ID: 1097831p21 RAS:GTP [plasma membrane]p21 RAS:GTPReactome DB_ID: 294381Converted from EntitySet in ReactomeReactome DB_ID: 96497151Reactome Database ID Release 71109783Database 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=109783ReactomeR-HSA-1097832Reactome 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-HSA-109783.2Reactome DB_ID: 294201Reactome Database ID Release 718941628Database 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=8941628ReactomeR-HSA-89416282Reactome 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-HSA-8941628.29632781Pubmed1998Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiationHadari, YRKouhara, HLax, ISchlessinger, JMol Cell Biol 18:3966-7317227708Pubmed2007The role of Shp2 (PTPN11) in cancerMohi, M GolamNeel, Benjamin GCurr. Opin. Genet. Dev. 17:23-3018452557Pubmed2008Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteinsGotoh, NCancer Sci 99:1319-25ACTIVATIONReactome Database ID Release 718948405Database 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=8948405ReactomeR-HSA-89484051Reactome 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-HSA-8948405.1Reactome DB_ID: 5654312Activated FGFR3:p-FRS:p-PTPN11 [plasma membrane]Activated FGFR3:p-FRS:p-PTPN11Converted from EntitySet in ReactomeReactome DB_ID: 56543051Activated FGFR3:p-FRS [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1625731UniProt:Q06124 PTPN11PTPN11PTP2CSHPTP2PTPN11FUNCTION Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73 (PubMed:26742426).SUBUNIT Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 (By similarity). Interacts with MILR1 (tyrosine-phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with PDGFRA (tyrosine phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts with GAB2. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1 and FER. Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts with GAREM1 isoform 1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation. Interacts with CDC73 (PubMed:26742426). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (By similarity). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (By similarity). Interacts with FCRL3 (via phosphorylated ITIM motifs) (PubMed:11162587, PubMed:19843936).TISSUE SPECIFICITY Widely expressed, with highest levels in heart, brain, and skeletal muscle.DOMAIN The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme.PTM Phosphorylated on Tyr-546 and Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated upon activation of the receptor-type kinase PDGFRA (By similarity). Phosphorylated by activated PDGFRB.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.UniProtQ06124O4'-phospho-L-tyrosine at 546546EQUALO4'-phospho-L-tyrosine [MOD:00048]O4'-phospho-L-tyrosine at 584584EQUALChain Coordinates1EQUAL597EQUALReactome Database ID Release 715654312Database 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=5654312ReactomeR-HSA-56543121Reactome 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-HSA-5654312.1