Left-hand side: the catalytic cycle of Prdx, exemplified by S. pombe Tpx1, involves the sulfenylated (SO−) peroxidatic cysteine (C48) forming a disulfide bond with a resolving cysteine (C170) in another Tpx1 subunit that is reduced by thioredoxin (Trx1red). Oxidized thioredoxin (Trx1ox) is reduced by thioredoxin reductase (TR) using electrons from NADPH. Alternatively, Prdx can form disulfide bonds with cysteines in other proteins, for example, components of P38 MAPK signaling pathways, e.g., Sty1 (P38) or ASK1. Right-hand side: the activity of the S. pombe Sty1 and mammalian P38 mitogen-activated protein kinase (MAPK) is regulated by phosphorylation and dephosphorylation of conserved threonine (T) and tyrosine (Y) residues by MAPK kinases (MAPKK) and MAPK tyrosine phosphatases (MKP/Pyp), respectively. MAPK kinase kinases (MAP3K) activate MAPKK by phosphorylating conserved serine (S) and threonine (T) residues. Mcs4 is required for MAP3K activity in S. pombe.
