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. a09 d07 c22 a36 f294c c41 bb5 f85 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9261 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2885 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:7186 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8550 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:3315 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6464 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5608 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4293 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5879 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:7046 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4209 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1386 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6772 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1385 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4217 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8569 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6885 receptor (TNFRSF)-interacting serine-threonine kinase 1 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8737 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9252 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1432 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2002 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4149 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1432 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:3265 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:998 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:3150 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5321 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6416 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1649 PDZ domain containing guanine nucleotide exchange Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5923 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9261 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:7042 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1616 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4214 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:4609 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8717 Translocate Translocate p38 MAPK signaling pathway PW:0000198 Pathway Ontology 10498912 PubMed p38 MAPK signalling cascades in inflammatory disease. Mol Med Today 1999 Herlaar E Brown Z 10557099 PubMed From receptors to stress-activated MAP kinases. Oncogene 1999 Ichijo H 10207619 PubMed Making 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 Symp 1999 Kyriakis JM 11163208 PubMed Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Mol Cell 2000 Lewis TS Hunt JB Aveline LD Jonscher KR Louie DF Yeh JM Nahreini TS Resing KA Ahn NG 10527909 PubMed Cell-type-specific activation of p38 protein kinase cascades by the novel tumor promoter palytoxin. Toxicol Appl Pharmacol 1999 Li S Wattenberg EV 10067858 PubMed Activation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone. Endocrinology 1999 Roberson MS Zhang T Li HL Mulvaney JM 10487205 PubMed The stress-activated protein kinase pathways. Cell Mol Life Sci 1999 Tibbles LA Woodgett JR 10097111 PubMed Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression. Proc Natl Acad Sci U S A 1999 Wysk M Yang DD Lu HT Flavell RA Davis RJ