Reference - PMID:37572670 - A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms.
Reference summary
- PubMed ID
- PMID:37572670
- Title
- A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms.
- Authors
- Cao M, Day AM, Galler M, Latimer HR, Byrne DP, Foy TW, Dwyer E, Bennett E, Palmer J, Morgan BA, Eyers PA, Veal EA
- Citation
- Mol Cell 2023 Sep 07;83(17):3140-3154.e7
- Publication year
- 2023
- Abstract
- Peroxiredoxins (Prdxs) utilize reversibly oxidized cysteine residues to reduce peroxides and promote H 2 O 2 signal transduction, including H 2 O 2 -induced activation of P38 MAPK. Prdxs form H 2 O 2 -induced disulfide complexes with many proteins, including multiple kinases involved in P38 MAPK signaling. Here, we show that a genetically encoded fusion between a Prdx and P38 MAPK is sufficient to hyperactivate the kinase in yeast and human cells by a mechanism that does not require the H 2 O 2 -sensing cysteine of the Prdx. We demonstrate that a P38-Prdx fusion protein compensates for loss of the yeast scaffold protein Mcs4 and MAP3K activity, driving yeast into mitosis. Based on our findings, we propose that the H 2 O 2 -induced formation of Prdx-MAPK disulfide complexes provides an alternative scaffold and signaling platform for MAPKK-MAPK signaling. The demonstration that formation of a complex with a Prdx is sufficient to modify the activity of a kinase has broad implications for peroxide-based signal transduction in eukaryotes.
Orthologs
- PRDX1 (HGNC:9352) Homo sapiens
- PRDX2 (HGNC:9353) Homo sapiens
