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 glucose 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 functions to alter its level of expression. PEA-15 is a widely expressed death effector domain-containing phosphoprotein involved in signal transduction, apoptosis, ERK activation, and glucose transport. The PLD1-interacting site on PEA-15 consists of part of the death effector domain domain plus additional C-terminal flanking sequences, whereas the PEA-15-interacting site on PLD1 overlaps the previously identified RhoA-interacting site. PEA-15 did not affect basal or stimulated in vitro PLD1 enzymatic activation. However, co-expression 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 present. PEA-15 similarly increased protein expressions level of PLD2 and co-immunoprecipitated with it. These results suggest that PEA-15 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 functional significance.
Department of Pharmacology and the Institute for Cell and Developmental Biology, SUNY at Stony Brook, Stony Brook, New York 11794-8651, USA.
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Y
Zhang
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O
Redina
Y M
YM
Altshuller
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Yamazaki
J
J
Ramos
H
H
Chneiweiss
Y
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Kanaho
M A
MA
Frohman
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D001692:Biological Transport; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D020798:Two-Hybrid System Techniques
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D020928:Mitogen-Activated Protein Kinases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D005947:Glucose