Bennett E

Byrne DP

Cao M

Day AM

Dwyer E

Eyers PA

Foy TW

Galler M

Latimer HR

Morgan BA

Palmer J

Veal EA

\ua9 2023 Peroxiredoxins (Prdxs) utilize reversibly oxidized cysteine residues to reduce peroxides and promote H2O2 signal transduction, including H2O2-induced activation of P38 MAPK. Prdxs form H2O2-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 H2O2-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 H2O2-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

Newcastle University E-Prints

A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms

A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms

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