The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli.
Source: KEGG http://www.genome.jp/dbget-bin/www_bget?pathway:map04010
Comments
HomologyMapper
This pathway was inferred from Homo sapiens pathway WP382 (r95114) with a 82.0% conversion rate.
Zhu X, Lee HG, Raina AK, Perry G, Smith MA; ''The role of mitogen-activated protein kinase pathways in Alzheimer's disease.''; Neurosignals, 2002 PubMedEurope PMCScholia
Takeda K, Ichijo H; ''Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system.''; Genes Cells, 2002 PubMedEurope PMCScholia
Tanoue T, Nishida E; ''Docking interactions in the mitogen-activated protein kinase cascades.''; Pharmacol Ther, 2002 PubMedEurope PMCScholia
Huang EJ, Reichardt LF; ''Trk receptors: roles in neuronal signal transduction.''; Annu Rev Biochem, 2003 PubMedEurope PMCScholia
Yang SH, Sharrocks AD, Whitmarsh AJ; ''Transcriptional regulation by the MAP kinase signaling cascades.''; Gene, 2003 PubMedEurope PMCScholia
Cho H, Lee J, Kwak NJ, Lee KH, Rha S, Kim YH, Cho YY, Yang KH, Kim K, Lim Y; ''Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line.''; Toxicol Lett, 2003 PubMedEurope PMCScholia
Harper SJ, LoGrasso P; ''Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38.''; Cell Signal, 2001 PubMedEurope PMCScholia
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S; ''MAPK pathways in radiation responses.''; Oncogene, 2003 PubMedEurope PMCScholia
Abell AN, Granger DA, Johnson GL; ''MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta.''; J Biol Chem, 2007 PubMedEurope PMCScholia
Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, Lu CS, Wang HL; ''(G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD.''; Cell Death Differ, 2012 PubMedEurope PMCScholia
Try the New WikiPathways
View approved pathways at the new wikipathways.org.Quality Tags
Ontology Terms
Bibliography
History
External references
DataNodes
Annotated Interactions
No annotated interactions