p38 MAPK signaling pathway (Homo sapiens)

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1-8Growth Factors, UVTrophic Factors, etc.?FASL, InflammatoryCytokines, UV, etc.Stress: Osmotic shockg-radiation, Anisomycin?Cytokines Production,Apoptosis, etc.?TranslationDNA transcription??GRB2RAC1PLA2G4ATGFBR1TRAF2SHC1MYCMAP3K1HMGN1MAP2K6MAP3K9ApoptosisMAPK14HSPB1TGFB2TRADDMAPKAPK2RPS6KA5MAPKAPK5CDC42RASGRF1MEF2DMAXMAP3K7MAP2K4MAP3K5MAPKAPK2HRASMAPK14ATF2DDIT3ELK1CREB1RIPK1MKNK1DAXXSTAT1Transcription factors


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 CPTAC Assay Portal.

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  1. Wysk M, Yang DD, Lu HT, Flavell RA, Davis RJ; ''Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression.''; Proc Natl Acad Sci U S A, 1999 PubMed Europe PMC Scholia
  2. Roberson MS, Zhang T, Li HL, Mulvaney JM; ''Activation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone.''; Endocrinology, 1999 PubMed Europe PMC Scholia
  3. Tibbles LA, Woodgett JR; ''The stress-activated protein kinase pathways.''; Cell Mol Life Sci, 1999 PubMed Europe PMC Scholia
  4. Kyriakis JM; ''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 PubMed Europe PMC Scholia
  5. Ichijo H; ''From receptors to stress-activated MAP kinases.''; Oncogene, 1999 PubMed Europe PMC Scholia
  6. Lewis TS, Hunt JB, Aveline LD, Jonscher KR, Louie DF, Yeh JM, Nahreini TS, Resing KA, Ahn NG; ''Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry.''; Mol Cell, 2000 PubMed Europe PMC Scholia
  7. Herlaar E, Brown Z; ''p38 MAPK signalling cascades in inflammatory disease.''; Mol Med Today, 1999 PubMed Europe PMC Scholia
  8. Li S, Wattenberg EV; ''Cell-type-specific activation of p38 protein kinase cascades by the novel tumor promoter palytoxin.''; Toxicol Appl Pharmacol, 1999 PubMed Europe PMC Scholia


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123111view06:57, 4 July 2022EgonwMade a pathway clickable
116725view10:05, 11 May 2021EweitzModified title
105865view23:23, 15 August 2019KhanspersModified description
95117view14:57, 16 November 2017Mkutmonremoved nested groups
72084view21:17, 24 October 2013Mkutmonadded datasource to "Apoptosis"
68934view17:34, 8 July 2013MaintBotUpdated to 2013 gpml schema
45281view19:07, 7 October 2011Khanspersremoved old comments
45280view19:06, 7 October 2011KhanspersOntology Term : 'p38 MAPK signaling pathway' added !
41085view23:20, 1 March 2011MaintBotRemoved redundant pathway information and comments
39751view06:40, 17 January 2011AlexanderPico
39698view08:32, 13 January 2011RameshELK1
39697view08:12, 13 January 2011RameshPeriodical save, work in progress
38775view23:52, 23 September 2010KhanspersChanged graphics and linked pathway
38238view21:16, 27 August 2010KhanspersRemoved receptor and protein complex graphics
38237view21:15, 27 August 2010Khanspers
34982view11:00, 9 February 2010Thomasmoved references in comment to bibliography
34981view10:52, 9 February 2010ThomasModified description
34980view10:51, 9 February 2010Thomasremoved "click for comments" label (leftover from GenMAPP version)
32421view17:09, 15 August 2009MaintBotFixed text labels
32079view13:39, 14 August 2009MaintBotFixed group labels
21524view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:p38 MAPK signaling pathway]] moved to [[Pathway:WP400]]: Moved to stable identifier
13959view10:53, 20 May 2008Thomasadded connectors, converted multi-line labels
12984view10:59, 17 May 2008MaintBotSticky edges patch by Sjoerd
8324view13:46, 7 January 2008MaintBot[[Pathway:Human:p38 MAPK signaling pathway]] moved to [[Pathway:Homo sapiens:p38 MAPK signaling pathway]]: Renaming species
7780view16:17, 18 December 2007MaintBotfixed category names
7322view12:42, 4 November 2007MaintBotAdded categories to GPML
6408view22:18, 22 May 2007S.Burelgpml file for [[Human:p38_MAPK_signaling_pathway]]

External references


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NameTypeDatabase referenceComment
ATF2GeneProduct1386 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
CDC42GeneProduct998 (Entrez Gene)
CREB1GeneProduct1385 (Entrez Gene)
DAXXGeneProduct1616 (Entrez Gene)
DDIT3GeneProduct1649 (Entrez Gene)
ELK1GeneProduct2002 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
HMGN1GeneProduct3150 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
HSPB1GeneProduct3315 (Entrez Gene)
MAP2K4GeneProduct6416 (Entrez Gene)
MAP2K6GeneProduct5608 (Entrez Gene)
MAP3K1GeneProduct4214 (Entrez Gene)
MAP3K5GeneProduct4217 (Entrez Gene)
MAP3K7GeneProduct6885 (Entrez Gene)
MAP3K9GeneProduct4293 (Entrez Gene)
MAPK14GeneProduct1432 (Entrez Gene)
MAPKAPK2GeneProduct9261 (Entrez Gene)
MAPKAPK5GeneProduct8550 (Entrez Gene)
MAXGeneProduct4149 (Entrez Gene)
MEF2DGeneProduct4209 (Entrez Gene)
MKNK1GeneProduct8569 (Entrez Gene)
MYCGeneProduct4609 (Entrez Gene)
PLA2G4AGeneProduct5321 (Entrez Gene)
RAC1GeneProduct5879 (Entrez Gene)
RASGRF1GeneProduct5923 (Entrez Gene) PDZ domain containing guanine nucleotide exchange
RIPK1GeneProduct8737 (Entrez Gene) receptor (TNFRSF)-interacting serine-threonine kinase 1
RPS6KA5GeneProduct9252 (Entrez Gene)
SHC1GeneProduct6464 (Entrez Gene)
STAT1GeneProduct6772 (Entrez Gene)
TGFB2GeneProduct7042 (Entrez Gene)
TGFBR1GeneProduct7046 (Entrez Gene)
TRADDGeneProduct8717 (Entrez Gene)
TRAF2GeneProduct7186 (Entrez Gene)

Annotated Interactions

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