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]. a09 d07 c22 a36 cae c41 bb5 f85 receptor (TNFRSF)-interacting serine-threonine kinase 1 PDZ domain containing guanine nucleotide exchange Translocate Translocate 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 10557099 PubMed From receptors to stress-activated MAP kinases. Oncogene 1999 Ichijo H 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 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 10487205 PubMed The stress-activated protein kinase pathways. Cell Mol Life Sci 1999 Tibbles LA Woodgett JR 10498912 PubMed p38 MAPK signalling cascades in inflammatory disease. Mol Med Today 1999 Herlaar E Brown Z p38 MAPK signaling pathway PW:0000198 Pathway Ontology