p38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases of the Rho family (Rac, Rho, Cdc42). As with other MAPK cascades, the membrane-proximal component is a MAPKKK, typically a MEKK or a mixed lineage kinase (MLK). The MAPKKK phosphorylates and activated MKK3/5, the p38 MAPK kinase. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. P38 MAK is involved in regulation of Hsp27 and MAPKAP-2 and several transcription factors including ATF2, STAT1, THE Max/Myc complex, MEF-2, ELK-1 and indirectly CREB via activation of MSK1.This pathway was inferred from Homo sapiens pathway [http://wikipathways.org/instance/WP400_r95117 WP400 (r95117)] with a 100.0% conversion rate.a09d07c22a36f294cc41bb5f85Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9261Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2885Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:7186Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8550Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:3315Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6464Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5608Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4293Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5879Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:7046Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4209Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1386Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6772Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1385Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4217Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8569Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6885receptor (TNFRSF)-interacting serine-threonine kinase 1Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8737Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9252Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1432Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2002Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4149Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1432Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:3265Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:998Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:3150Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5321Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6416Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1649PDZ domain containing guanine nucleotide exchangeHomology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5923Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9261Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:7042Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1616Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4214Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4609Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8717TranslocateTranslocatep38 MAPK signaling pathwayPW:0000198Pathway Ontology10498912PubMedp38 MAPK signalling cascades in inflammatory disease.Mol Med Today1999Herlaar EBrown Z10557099PubMedFrom receptors to stress-activated MAP kinases.Oncogene1999Ichijo H10207619PubMedMaking the connection: coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase) core signalling modules to extracellular stimuli and biological responses.Biochem Soc Symp1999Kyriakis JM11163208PubMedIdentification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry.Mol Cell2000Lewis TSHunt JBAveline LDJonscher KRLouie DFYeh JMNahreini TSResing KAAhn NG10527909PubMedCell-type-specific activation of p38 protein kinase cascades by the novel tumor promoter palytoxin.Toxicol Appl Pharmacol1999Li SWattenberg EV10067858PubMedActivation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone.Endocrinology1999Roberson MSZhang TLi HLMulvaney JM10487205PubMedThe stress-activated protein kinase pathways.Cell Mol Life Sci1999Tibbles LAWoodgett JR10097111PubMedRequirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression.Proc Natl Acad Sci U S A1999Wysk MYang DDLu HTFlavell RADavis RJ