Peroxiredoxin II functions as a signal terminator for H2O2-activated phospholipase D1.

Phospholipase D1 (PLD1) is a signal-transduction regulated enzyme which regulates several cell intrinsic processes including activation of NAPDH oxidase, which elevates intracellular H2O2. Several proteins have been reported to interact with PLD1 in resting cells. We sought to identify proteins that interact with PLD1 after phorbol 12-myristate 13-acetate (PMA) stimulation. A novel interaction with peroxiredoxin II (PrxII), an enzyme that eliminates cellular H2O2, which is a known stimulator of PLD1, was identified by PLD1-affinity pull-down and MS. PMA stimulation was confirmed to promote physical interaction between PLD1 and PrxII and to cause PLD1 and PrxII to colocalize subcellularly. Functional significance of the interaction was suggested by the observation that over-expression of PrxII specifically reduces the response of PLD1 to stimulation by H2O2. These results indicate that PrxII may have a signal-terminating role for PLD1 by being recruited to sites containing activated PLD1 after cellular stimulation involving production of H2O2.