BioPAX pathway converted from "ERKs are inactivated" in the Reactome database. ERKs are inactivated ERKs are inactivated 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> 3.1.3.16 ERKs are inactivated by protein phosphatase 2A ERKs are inactivated by protein phosphatase 2A 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> Reactome DB_ID: 113518 1 nucleoplasm GO 0005654 water [ChEBI:15377] water Reactome http://www.reactome.org ChEBI 15377 Reactome DB_ID: 10632613 1 p-Y185,Y187 MAPK1 dimer [nucleoplasm] p-Y185,Y187 MAPK1 dimer Reactome DB_ID: 10628758 2 UniProt:P40417 rl Drosophila melanogaster NCBI Taxonomy 7227 UniProt P40417 O-phospho-L-threonine at 185 (in Homo sapiens) 185 EQUAL O-phospho-L-threonine [MOD:00047] O4'-phospho-L-tyrosine at 187 (in Homo sapiens) 187 EQUAL O4'-phospho-L-tyrosine [MOD:00048] Chain Coordinates 2 EQUAL 360 EQUAL Reactome Database ID Release 81 10632613 Database 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=10632613 Reactome R-DME-109856 1 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-DME-109856.1 Reactome DB_ID: 10632940 1 MAPK1 dimer [nucleoplasm] MAPK1 dimer Reactome DB_ID: 10632938 2 2 EQUAL 360 EQUAL Reactome Database ID Release 81 10632940 Database 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=10632940 Reactome R-DME-5675356 1 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-DME-5675356.1 Reactome DB_ID: 113550 1 hydrogenphosphate [ChEBI:43474] hydrogenphosphate [PO3(OH)](2-) HYDROGENPHOSPHATE ION hydrogen phosphate [P(OH)O3](2-) HPO4(2-) phosphate INORGANIC PHOSPHATE GROUP ChEBI 43474 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10632944 PP2A-ABdeltaC complex [nucleoplasm] PP2A-ABdeltaC complex Converted from EntitySet in Reactome Reactome DB_ID: 10626570 1 PP2A-catalytic subunit C [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Converted from EntitySet in Reactome Reactome DB_ID: 10626578 1 PP2A-subunit A [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 10632942 1 UniProt:Q8IN89 wrd UniProt Q8IN89 1 EQUAL 602 EQUAL Reactome Database ID Release 81 10632944 Database 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=10632944 Reactome R-DME-165970 1 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-DME-165970.1 GO 0004722 GO molecular function Reactome Database ID Release 81 10632945 Database 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=10632945 Reactome Database ID Release 81 10632947 Database 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=10632947 Reactome R-DME-199959 1 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-DME-199959.1 ERKs are inactivated by the protein phosphatase 2A (PP2A). The PP2A holoenzyme is a heterotrimer that consists of a core dimer, composed of a scaffold (A) and a catalytic (C) subunit that associates with a variety of regulatory (B) subunits. The B subunits have been divided into gene families named B (or PR55), B0 (or B56 or PR61) and B00 (or PR72). Each family comprises several members. B56 family members of PP2A in particular, increase ERK dephosphorylation, without affecting its activation by MEK.<br>Induction of PP2A is involved in the extracellular signal-regulated kinase (ERK) signalling pathway, in which it provides a feedback control, as well as in a broad range of other cellular processes, including transcriptional regulation and control of the cell cycle.This diversity of functions is conferred by a diversity of regulatory subunits, the combination of which can give rise to over 50 different forms of PP2A. For example, five distinct mammalian genes encode members of the B56 family, called B56a, b, g, d and e, generating at least eight isoforms. Whether a specific holoenzyme dephosphorylates ERK and whether this activity is controlled during mitogenic stimulation is unknown. 16456541 Pubmed 2006 B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK Letourneux, C Rocher, G Porteu, F EMBO J 25:727-38 inferred by electronic annotation IEA GO IEA 3.1.3.48 ERKs are inactivated by dual-specific phosphatases (DUSPs) ERKs are inactivated by dual-specific phosphatases (DUSPs) 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> Reactome DB_ID: 113518 1 Reactome DB_ID: 10632613 1 Reactome DB_ID: 10632940 1 Reactome DB_ID: 113550 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10633902 ERK-specific DUSP [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity MKP-like [nucleoplasm] Mkp3 [nucleoplasm] UniProt X2JEB8 UniProt Q9VVW5 GO 0004725 GO molecular function Reactome Database ID Release 81 10633903 Database 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=10633903 Reactome Database ID Release 81 10633919 Database 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=10633919 Reactome R-DME-203797 1 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-DME-203797.1 Over 10 dual specificity phosphatases (DUSPs) active on MAP kinases are known. Among them, some possess good ERK docking sites and so are more specific for the ERKS (DUSP 3, 4, 6, 7), others are more specific for p38MAPK (DUSP1 and 10), while others do not seem to discriminate. It is noteworthy that transcription of DUSP genes is induced by growth factor signaling itself, so that these phosphatases provide feedback attenuation of signaling. Moreover, differential activation of DUSPs by different stimuli is thought to contribute to pathway specificity. 17322878 Pubmed 2007 A module of negative feedback regulators defines growth factor signaling Amit, I Citri, A Shay, T Lu, Y Katz, M Zhang, F Tarcic, G Siwak, D Lahad, J Jacob-Hirsch, J Amariglio, N Vaisman, N Segal, E Rechavi, G Alon, U Mills, GB Domany, E Yarden, Y Nat Genet 39:503-12 inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 81 10633920 Database 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=10633920 Reactome DB_ID: 10633917 VRK3:DUSP3 [nucleoplasm] VRK3:DUSP3 Reactome DB_ID: 10633893 1 UniProt:X2JEB8 MKP-like 1 EQUAL 185 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10633915 1 Homologues of VRK3 [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ball [nucleoplasm] BcDNA.LD23371 [nucleoplasm] UniProt Q7KRY6 UniProt Q7KMI3 Reactome Database ID Release 81 10633917 Database 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=10633917 Reactome R-DME-8942511 1 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-DME-8942511.1 Reactome Database ID Release 81 10696673 Database 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=10696673 Reactome R-DME-202670 1 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-DME-202670.1 MAP Kinases are inactivated by a family of protein named MAP Kinase Phosphatases (MKPs). They act through dephosphorylation of threonine and/or tyrosine residues within the signature sequence -pTXpY- located in the activation loop of MAP kinases (pT=phosphothreonine and pY=phosphotyrosine). MKPs are divided into three major categories depending on their preference for dephosphorylating; tyrosine, serine/threonine and both the tyrosine and threonine (dual specificity phoshatases or DUSPs). The tyrosine-specific MKPs include PTP-SL, STEP and HePTP, serine/threonine-specific MKPs are PP2A and PP2C, and many DUSPs acting on MAPKs are known. Activated MAP kinases trigger activation of transcription of MKP genes. Therefore, MKPs provide a negative feedback regulatory mechanism on MAPK signaling, by inactivating MAPKs via dephosphorylation, in the cytoplasm and the nucleus. Some MKPs are more specific for ERKs, others for JNK or p38MAPK. 15115656 Pubmed 2004 Structure and regulation of MAPK phosphatases Farooq, A Zhou, MM Cell Signal 16:769-79 inferred by electronic annotation IEA GO IEA