Pea15

Phosphoprotein enriched in astrocytes of 15 kilodaltons (PEA-15a) is a death-effector domain-containing protein that is reported to regulate apoptosis, proliferation, glucose transport, adhesion and migration. PEA-15 binds a diverse set of signal transduction proteins that are responsible for these functions. Among the better-characterized interactions are those with extracellular signal-regulated kinase (ERK), Fas-associated death domain protein (FADD), p90 ribosomal S6 protein kinase 2 (RSK2), Akt, phospholipase D1 (PLD1) and the pro-apoptotic serine-directed protease Omi/HtrA2. PEA-15 is phosphorylated at two serine residues (Ser 104 and Ser 116) by protein kinase C α (PKCα) and either calcium/calmodulin-dependent protein kinase II (CaMKII), PKCζ or Akt, respectively, and phosphorylation regulates ERK and FADD binding. Finally, PEA-15 expression is upregulated in some breast cancers and gliomas as well as in type 2 diabetes. PEA-15 expression is downregulated in invasive astrocytomas and breast cancer cells.