Host-pathogen interaction of human coronaviruses - MAPK signaling (WP4877)
Homo sapiens
This pathway describes the activation of the human MAPK signaling system during human coronavirus infection, per Fung and Liu, Figure 7 [10.1146/annurev-micro-020518-115759]. The MAPK signaling system regulates response to different environmental stimuli, e.g. inflammation due to infection. Its downstream effects include regulation of cell cycle, apoptosis, differentiation and immune response. During coronavirus infection, three MAPK signaling pathways were studied and described. The p38 pathway (MAPK11 - MAPK14) leads to stimulation of apoptosis via CHOP (DDIT3) while the ERK pathway (MAPK1 and MAPK3) counteracts apoptosis stimulation and supports cell survival by stimulating ATF2 and FOS. The JNK pathway (MAPK 8 - MAPK10) inhibits cell survival protein BCL2, thus stimulating apoptosis but also stimulating the AP1 complex that leads to the production of effectors to fight the infection. The interplay of apoptosis stimulation and cell survival is not yet fully understood in SARS-CoV-2 infection.
Authors
Friederike Ehrhart , Egon Willighagen , Alex Pico , Rex D A B , Kristina Hanspers , Marvin Martens , Martina Summer-Kutmon , Eric Weitz , Finterly Hu , Denise Slenter , and Isabel WassinkActivity
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Cited In
- Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions (2022).
- A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis (2024).
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Organisms
Homo sapiensCommunities
COVID-19Annotations
Pathway Ontology
signaling pathway p38 MAPK signaling pathwayDisease Ontology
viral infectious disease severe acute respiratory syndrome COVID-19| Label | Type | Compact URI | Comment |
|---|---|---|---|
| MAP3K1 | GeneProduct | ensembl:ENSG00000095015 | MEKK1 |
| MAP3K9 | GeneProduct | ensembl:ENSG00000006432 | MLK1 |
| MAP3K10 | GeneProduct | ensembl:ENSG00000130758 | MLK2 |
| MAP3K11 | GeneProduct | ensembl:ENSG00000173327 | MLK3 |
| MAPK9 | GeneProduct | ncbigene:5601 | JNK |
| JUN | GeneProduct | ensembl:ENSG00000177606 | AP1 |
| FOS | GeneProduct | ensembl:ENSG00000170345 | AP1 |
| MAPK11 | GeneProduct | ncbigene:5600 | p38 |
| MAPK13 | GeneProduct | ncbigene:5603 | p38 |
| DDIT3 | GeneProduct | ensembl:ENSG00000175197 | CHOP |
| MAPK12 | GeneProduct | ncbigene:6300 | p38 |
| MAP3K4 | GeneProduct | ensembl:ENSG00000085511 | MEKK4 |
| MAPK3 | GeneProduct | ncbigene:5595 | ERK1 |
| MAP2K7 | GeneProduct | ensembl:ENSG00000076984 | MKK7 |
| MAPK1 | GeneProduct | ncbigene:5594 | ERK2 |
| ATF2 | GeneProduct | ensembl:ENSG00000115966 | |
| MAPK8 | GeneProduct | ncbigene:5599 | JNK |
| MAP2K4 | GeneProduct | ensembl:ENSG00000065559 | MKK4 |
| MAP2K3 | GeneProduct | ensembl:ENSG00000034152 | MKK3 |
| EIF4E | GeneProduct | ensembl:ENSG00000151247 | |
| MAPK14 | GeneProduct | ensembl:ENSG00000112062 | p38 |
| MAP2K1 | GeneProduct | ensembl:ENSG00000169032 | MKK1 |
| RPS6KA3 | GeneProduct | ensembl:ENSG00000177189 | RSK |
| FOS | GeneProduct | ensembl:ENSG00000170345 | c-FOS |
| BCL2 | GeneProduct | ensembl:ENSG00000171791 | |
| MAPK10 | GeneProduct | ncbigene:5602 | JNK |
| RPS6KA2 | GeneProduct | ensembl:ENSG00000071242 | RSK |
| MAP2K6 | GeneProduct | ensembl:ENSG00000108984 | MKK6 |
| MAP2K2 | GeneProduct | ensembl:ENSG00000126934 | MKK2 |
| RPS6KA1 | GeneProduct | ensembl:ENSG00000117676 | RSK |
| RAF1 | GeneProduct | ensembl:ENSG00000132155 | |
| IFI27 | GeneProduct | ncbigene:3429 | |
| BST2 | GeneProduct | ncbigene:684 | |
| JUNB | GeneProduct | ncbigene:3726 | |
| S | Protein | wikidata:Q89458416 | |
| orf3a | Protein | uniprot:P59632 | |
| orf3b | Protein | uniprot:P59633 | |
| orf7a | Protein | uniprot:P59635 | |
| N | Protein | wikidata:Q89457519 | |
| orf6 | Protein | uniprot:P59634 | |
| IFITM2 | Protein | ensembl:ENSG00000185201 | |
| IFITM3 | Protein | ensembl:ENSG00000142089 | |
| IFITM1 | Protein | ensembl:ENSG00000185885 |
References
- Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19 [Internet]. Huang L, Shi Y, Gong B, Jiang L, Liu X, Yang J, et al. Cold Spring Harbor Laboratory; 2020. Available from: http://dx.doi.org/10.1101/2020.03.15.20033472 DOI Scholia
- Human Coronavirus: Host-Pathogen Interaction. Fung TS, Liu DX. Annu Rev Microbiol. 2019 Sep 8;73:529–57. PubMed Europe PMC Scholia