MAPK signaling and ARTD family members (WP5530)

Homo sapiens

The mitogen-activated protein kinase (MAPK) pathway is a series of cytoplasmic phosphorylation events triggered by the binding of mitogens, growth factors, and cytokines to their receptors. MAPK signaling effects on ARTD family members ERK signaling positively regulates both the expression and activity of PARP1. When MEK, the kinase upstream of ERK in the MAPK cascade, was inhibited in conditioned medium-stimulated endothelial cells, it decreased PARP1 expression. On the other hand, overexpressing p-ERK2 in neurons led to an increase in PARP1 activity. ERK signaling also influences Tankyrase 1 activity. In 3T3-L1 fibroblasts and adipocytes stimulated by insulin, PDGF, and EGF, ERK phosphorylates Tankyrase 1. JNK1 has been suggested as a positive regulator of PARP1 activation during H2O2-induced cell death in mouse embryonic fibroblasts (MEFs). In the context of multiple myeloma, JNK2 enhances PARP14 protein levels through an unknown mechanism. Positive regulation MAPK signaling is positively regulated by PARP1 and Tankyrase 1/2. Under normal conditions, phosphorylation of ERK1/2 (p-ERK1/2) by MEK1/2 (MAPKK) induces conformational changes that activate ERK1/2, leading to the phosphorylation of downstream targets that promote cell growth, survival, and migration. Perfusing rat hearts with a cytostatic agent increased cardiotoxicity and phosphorylation of ERK, JNK, and p38. Inhibition of PARP1-dependent ADP-ribosylation with BGP-15 significantly reduces MAPK phosphorylation. PARP1 activation also correlates with JNK and p38 signaling in various cell types, especially in the context of ROS-dependent PARP1 activation and cell death, which depends on JNK and/or p38 signaling. Although primarily observed in Drosophila melanogaster rather than mammalian cells, Tankyrase 1/2 have been implicated in JNK activation. Negative regulation In the case of Salmonella infection in human colonic epithelial cells, PARP inhibitor PJ-34 treatment increases ERK phosphorylation, NF-κB signaling, and IL-6 production/secretion, even at early time points. Inhibition of PARP1 increased ERK activation and reduced cell death in H2O2-induced apoptosis of human WRL-68 cells, while simultaneously lowering p-JNK and p-p38 levels. PARP14 interacts with and likely ADP-ribosylate JNK1, inhibiting its kinase activity and reducing JNK1-dependent apoptosis. Similarly, inhibition of PARP14 with PJ-34 leads to increased JNK1 activity and enhanced cell death.

Authors

Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

mitogen activated protein kinase signaling pathway

Participants

Label Type Compact URI Comment
MAP2K1 GeneProduct ensembl:ENSG00000169032 'MEK1/2' in source
MAPK3 GeneProduct ensembl:ENSG00000102882 'ERK1/2' in source
TNKS GeneProduct ensembl:ENSG00000173273 'TNKS1' in source
PARP1 GeneProduct ensembl:ENSG00000143799
PARP14 GeneProduct ensembl:ENSG00000173193
MAP2K4 GeneProduct ensembl:ENSG00000065559 'MKK4/7'
MAPK14 GeneProduct ensembl:ENSG00000112062 'p38a/b/g/d' in source
MAPK8 GeneProduct ensembl:ENSG00000107643 'JNK1-3' in source
DUSP1 GeneProduct ensembl:ENSG00000120129 'MKP-1' in source
ATF4 GeneProduct ensembl:ENSG00000128272
MAP2K3 GeneProduct ensembl:ENSG00000034152 'MKK3/4/6' in source
MAP2K4 GeneProduct ensembl:ENSG00000065559 'MKK3/4/6' in source
MAP2K6 GeneProduct ensembl:ENSG00000108984 'MKK3/4/6' in source
MAP2K7 GeneProduct ensembl:ENSG00000076984 'MKK4/7' in source
MAP2K2 GeneProduct ensembl:ENSG00000126934 'MEK1/2' in source
MAPK1 GeneProduct ensembl:ENSG00000100030 'ERK1/2' in source
MAPK9 GeneProduct ensembl:ENSG00000050748 'JNK1-3' in source
MAPK10 GeneProduct ensembl:ENSG00000109339 'JNK1-3' in source
MAPK11 GeneProduct ensembl:ENSG00000185386 'p38a/b/g/d' in source
MAPK12 GeneProduct ensembl:ENSG00000188130 'p38a/b/g/d' in source
MAPK13 GeneProduct ensembl:ENSG00000156711 'p38a/b/g/d' in source
BRAF GeneProduct ensembl:ENSG00000157764 'Rafs / Mos' in source
RAF1 GeneProduct ensembl:ENSG00000132155 'Rafs / Mos' in source
ARAF GeneProduct ensembl:ENSG00000078061 'Rafs / Mos' in source
MAP3K5 GeneProduct ensembl:ENSG00000197442 'MAPKKK' in source / 'ASK' in source
MAP3K12 GeneProduct ensembl:ENSG00000139625 'MAPKKK' in source, 'DLK' in source
MAP3K1 GeneProduct ensembl:ENSG00000095015 'MAPKKK' in source, 'MEKK' in source
MAP3K9 GeneProduct ensembl:ENSG00000006432 'MAPKKK' in source, 'MLK' in source
MAP3K7 GeneProduct ensembl:ENSG00000135341 'MAPKKK' in source, 'TAK1' in source
MAP3K8 GeneProduct ensembl:ENSG00000107968 'MAPKKK' in source, 'TLP2' in source
MAP3K10 GeneProduct ensembl:ENSG00000130758 'MAPKKK' in source, 'MLK' in source
MAP3K11 GeneProduct ensembl:ENSG00000173327 'MAPKKK' in source, 'MLK' in source
MAP3K21 GeneProduct ensembl:ENSG00000143674 'MAPKKK' in source, 'MLK' in source

References

  1. Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses. Boehi F, Manetsch P, Hottiger MO. Cell Discov. 2021 Nov 2;7(1):104. PubMed Europe PMC Scholia