Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them

Phospholipase D (PLD), a signal-transducing membrane-associated enzyme, is implicated in diverse processes including apoptosis, ERK activation, and gl ucose transport, Prior studies have identified specific PLD activators and repressors that directly regulate its enzymatic activity. Using two-hybrid screens, we have identified PEA-15 as a PLD interactor that unexpectedly fu nctions to:alter its level of expression. PEA-15 is a widely expressed deat h effector domain-containing phosphoprotein involved in signal transduction , apoptosis,:ERK activation, and glucose transport. The PLD1-interacting si te on PEA-15 consists of part of the death effector domain domain plus addi tional C-terminal flanking:sequences, whereas the PEA-15-interacting site o n:PLD1 overlaps the previously identified RhoA-interacting site. PEA-15 did not affect basal or stimulated;in vitro PLD1 enzymatic activation. However , coexpression of PEA-15 increased levels of PLD1 activity. This increased activation correlated with higher PLD1 protein expression levels, as marked by faster accumulation and longer persistence of PLD1 when PEA-15 was pres ent; PEA-15 similarly increased protein expressions level of PLDS and co-im munoprecipitated with it. These results: suggest that PEA-IB may stabilize PLD or act as a PLD chaperone. The common involvement of PEA-15 and PLD in, :apoptosis, ERK activation, and glucose transport additionally suggests fun ctional significance.