Reactome: A Curated Pathway Database

ERKs are inactivated (R-HSA-202670) [Homo sapiens]


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.

Locations in the PathwayBrowser
Cross References
Database Identifier
BioModels Database BIOMD0000000175, BIOMD0000000557, BIOMD0000000255, BIOMD0000000251
Literature References
pubMedId Title Journal Year
15115656 Structure and regulation of MAPK phosphatases Cell Signal 2004
17322878 A module of negative feedback regulators defines growth factor signaling Nat Genet 2007