p38 MAPK signaling (WP400)

Homo sapiens

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].

Authors

Sebastien Burel , Thomas Kelder , Kristina Hanspers , Ramesh , Alex Pico , Martina Summer-Kutmon , Eric Weitz , and Egon Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

p38 MAPK signaling pathway

Participants

Label Type Compact URI Comment
MAPKAPK2 GeneProduct ncbigene:9261
GRB2 GeneProduct ncbigene:2885
TRAF2 GeneProduct ncbigene:7186
MAPKAPK5 GeneProduct ncbigene:8550
HSPB1 GeneProduct ncbigene:3315
SHC1 GeneProduct ncbigene:6464
MAP2K6 GeneProduct ncbigene:5608
MAP3K9 GeneProduct ncbigene:4293
RAC1 GeneProduct ncbigene:5879
TGFBR1 GeneProduct ncbigene:7046
MEF2D GeneProduct ncbigene:4209
ATF2 GeneProduct ncbigene:1386
STAT1 GeneProduct ncbigene:6772
CREB1 GeneProduct ncbigene:1385
MAP3K5 GeneProduct ncbigene:4217
MKNK1 GeneProduct ncbigene:8569
MAP3K7 GeneProduct ncbigene:6885
RIPK1 GeneProduct ncbigene:8737 receptor (TNFRSF)-interacting serine-threonine kinase 1
RPS6KA5 GeneProduct ncbigene:9252
MAPK14 GeneProduct ncbigene:1432
ELK1 GeneProduct ncbigene:2002
MAX GeneProduct ncbigene:4149
HRAS GeneProduct ncbigene:3265
CDC42 GeneProduct ncbigene:998
HMGN1 GeneProduct ncbigene:3150
PLA2G4A GeneProduct ncbigene:5321
MAP2K4 GeneProduct ncbigene:6416
DDIT3 GeneProduct ncbigene:1649
RASGRF1 GeneProduct ncbigene:5923 PDZ domain containing guanine nucleotide exchange
TGFB2 GeneProduct ncbigene:7042
DAXX GeneProduct ncbigene:1616
MAP3K1 GeneProduct ncbigene:4214
MYC GeneProduct ncbigene:4609
TRADD GeneProduct ncbigene:8717

References

  1. Activation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone. Roberson MS, Zhang T, Li HL, Mulvaney JM. Endocrinology. 1999 Mar;140(3):1310–8. PubMed Europe PMC Scholia
  2. Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression. Wysk M, Yang DD, Lu HT, Flavell RA, Davis RJ. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3763–8. PubMed Europe PMC Scholia
  3. 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. Kyriakis JM. Biochem Soc Symp. 1999;64:29–48. PubMed Europe PMC Scholia
  4. The stress-activated protein kinase pathways. Tibbles LA, Woodgett JR. Cell Mol Life Sci. 1999 Aug 15;55(10):1230–54. PubMed Europe PMC Scholia
  5. p38 MAPK signalling cascades in inflammatory disease. Herlaar E, Brown Z. Mol Med Today. 1999 Oct;5(10):439–47. PubMed Europe PMC Scholia
  6. Cell-type-specific activation of p38 protein kinase cascades by the novel tumor promoter palytoxin. Li S, Wattenberg EV. Toxicol Appl Pharmacol. 1999 Oct 15;160(2):109–19. PubMed Europe PMC Scholia
  7. From receptors to stress-activated MAP kinases. Ichijo H. Oncogene. 1999 Nov 1;18(45):6087–93. PubMed Europe PMC Scholia
  8. Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Lewis TS, Hunt JB, Aveline LD, Jonscher KR, Louie DF, Yeh JM, et al. Mol Cell. 2000 Dec;6(6):1343–54. PubMed Europe PMC Scholia