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.
Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP400 CPTAC Assay Portal].a09d07c22a36caec41bb5f85receptor (TNFRSF)-interacting serine-threonine kinase 1PDZ domain containing guanine nucleotide exchangeTranslocateTranslocate10067858PubMedActivation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone.Endocrinology1999Roberson MSZhang TLi HLMulvaney JM10557099PubMedFrom receptors to stress-activated MAP kinases.Oncogene1999Ichijo H10097111PubMedRequirement 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 RJ10207619PubMedMaking 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 EV10487205PubMedThe stress-activated protein kinase pathways.Cell Mol Life Sci1999Tibbles LAWoodgett JR10498912PubMedp38 MAPK signalling cascades in inflammatory disease.Mol Med Today1999Herlaar EBrown Zp38 MAPK signaling pathwayPW:0000198Pathway Ontology