BioPAX pathway converted from "PPTN11 dephosphorylates SPRY2" in the Reactome database.3.1.3.48PPTN11 dephosphorylates SPRY2PPTN11 dephosphorylates SPRY2This 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>Reactome DB_ID: 98693691plasma membraneGO0005886PPA2A (A:C):Y55/Y227 p-SPRY2:GRB2 [plasma membrane]PPA2A (A:C):Y55/Y227 p-SPRY2:GRB2Reactome DB_ID: 98265631cytosolGO0005829UniProt:P62994 Grb2Grb2AshGrb2FUNCTION Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.SUBUNIT Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect. Interacts with IRS4 (when Tyr-phosphorylated). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with phosphorylated MET. Interacts with phosphorylated TOM1L1. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1 and REPS2. Interacts with syntrophin SNTA1. Interacts (via SH3 domains) with REPS1. Interacts (via SH3 domains) with PIK3C2B. Interacts with CBL and CBLB. Interacts with AJUBA and CLNK. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Interacts with PTPN11. Interacts with PRNP. Interacts with RALGPS1. Interacts also with HCST. Interacts with KDR. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with GAPT and PTPRE. Interacts (via SH2 domain) with KIF26A. Interacts (via SH3 2) with GAB2. Interacts with ADAM15. Interacts with THEMIS2. Interacts (via SH2 domain) with AXL (phosphorylated). Interacts (via SH2 domain) with KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with PTPN23. Interacts with FLT4 (tyrosine phosphorylated). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. 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. Interacts with ERBB4. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts with PTK2B/PYK2 (tyrosine phosphorylated). Interacts (via SH2-domain) with SCIMP; this interaction is dependent on phosphorylation on SCIMP 'Tyr-58' (By similarity). Interacts (via SH3 domains) with GAREM1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation. Interacts with DAB2. Interacts with TESPA1. Interacts with THEMIS. Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1. Interacts with CD28. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts with ASAP3 (phosphorylated form) (By similarity). Interacts (via SH2 domain) with CSF1R and IRS1 (tyrosine phosphorylated) (PubMed:8262059, PubMed:8388384). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity). 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 Wide tissue distribution.DOMAIN The SH3 domains mediate interaction with RALGPS1 and SHB.SIMILARITY Belongs to the GRB2/sem-5/DRK family.Reactomehttp://www.reactome.orgRattus norvegicusNCBI Taxonomy10116UniProtP62994Chain Coordinates1EQUAL217EQUALReactome DB_ID: 98693641PP2A(A:C):Y55/Y227-pSPRY2 [plasma membrane]PP2A(A:C):Y55/Y227-pSPRY2Reactome DB_ID: 98619211PP2A (A:C) [cytosol]PP2A (A:C)Converted from EntitySet in ReactomeReactome DB_ID: 98619191PP2A (Calpha/Cbeta) [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityPpp2ca [cytosol]Ppp2cb [cytosol]UniProtP63331UniProtP62716Reactome DB_ID: 98311121UniProt:Q5XI34 Ppp2r1aPpp2r1aPpp2r1arCG_22961 <submittedName> <fullName>Protein phosphatase 2 (Formerly 2A), regulatory subunit A, alpha isoform</fullName> </submittedName> <submittedName> <fullName>Protein phosphatase 2 (Formerly 2A), regulatory subunit A (PR 65), alpha isoform, isoform CRA_a</fullName> </submittedName> UniProtQ5XI342EQUAL589EQUALReactome Database ID Release 759861921Database 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=9861921ReactomeR-RNO-9345441Reactome 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-RNO-934544.1Reactome DB_ID: 98619431UniProt:Q5HZA2Spry2UniProtQ5HZA2O4'-phospho-L-tyrosine at 55 (in Homo sapiens)55EQUALO4'-phospho-L-tyrosine [MOD:00048]O4'-phospho-L-tyrosine at 227 (in Homo sapiens)227EQUAL1EQUAL315EQUALReactome Database ID Release 759869364Database 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=9869364ReactomeR-RNO-9345981Reactome 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-RNO-934598.1Reactome Database ID Release 759869369Database 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=9869369ReactomeR-RNO-12956251Reactome 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-RNO-1295625.1Reactome DB_ID: 982656311EQUAL217EQUALReactome DB_ID: 98693641PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 548923UniProt:P41499 Ptpn11Ptpn11Ptpn11FUNCTION Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (By similarity). Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity. Dephosphorylates CDC73 (By similarity). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity).ACTIVITY REGULATION Inhibited by orthovanadate, molybdate and spermidine.SUBUNIT Interacts with phosphorylated SIT1, LIME1, BCAR3 and MZPL1. Interacts with FCRL4, FCRL6, ANKHD1, SHB, INPP5D/SHIP1 and CD84 (By similarity). Interacts with MILR1 (tyrosine-phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2 (By similarity). Interacts with PTPNS1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with GAB2 (By similarity). 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 PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity (By similarity). Interacts with ROS1; this mediates PTPN11 phosphorylation. 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) (By similarity). Interacts with SIGLEC10 (By similarity).TISSUE SPECIFICITY Expressed in brain, muscle and lung.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-542 and Tyr-580 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. Phosphorylated by activated PDGFRB (By similarity).SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.UniProtP414991EQUAL597EQUALGO0004725GO molecular functionReactome Database ID Release 759867102Database 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=9867102Reactome Database ID Release 759872769Database 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=9872769ReactomeR-RNO-15495641Reactome 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-RNO-1549564.1PPTN11 (also known as SHP2) may exert its positive effects on MAPK activation in response to FGF stimulation by catalyzing the dephosphorylation of tyrosine resides on SPRY2. This dephosphorylation promotes dissociation of the GRB2/SPRY2 complex and as a consequence stimulates GRB2 association with the activated receptor, leading to sustained MAPK signaling.17993263Pubmed2008The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathwayDance, MMontagner, ASalles, JPYart, ARaynal, PCell Signal 20:453-915031289Pubmed2004Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor SproutyHanafusa, HTorii, SYasunaga, TMatsumoto, KNishida, EJ Biol Chem 279:22992-5inferred by electronic annotationIEAGOIEA