Phosphoprotein enriched in astrocytes 15 kDa (PEA-15)

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a widely expressed cytoplasmic phosphoprotein originally identified in astrocytes but also present in neurons and other cell types[5]. It plays a critical role as a signaling scaffold, notably by binding extracellular signal-regulated kinases 1 and 2 (ERK1/2) and modulating their subcellular localization, thereby influencing cell proliferation—unphosphorylated PEA-15 inhibits ERK1/2 nuclear translocation and suppresses proliferation, while phosphorylation of PEA-15 (at Ser104 and Ser116) releases this inhibition, allowing proliferation[1]. PEA-15 also regulates cell survival and apoptosis; it can inhibit apoptosis by sequestering Fas-associated death domain protein (FADD) away from the death-inducing signaling complex (DISC), thus blocking caspase-8 activation[1]. Additionally, PEA-15 inhibits astrocyte migration by suppressing the generation or activity of a 40-kDa form of protein kinase C delta (PKCδ), which is implicated in enhanced cell motility[3]. PEA-15 is subject to dynamic phosphorylation by several kinases, including PKC, Akt, and CaMKII, allowing it to shuttle between roles in proliferation, survival, and migration[1][4]. Overexpression of PEA-15 is associated with type 2 diabetes and has been implicated in cancer biology, particularly in the regulation of tumor cell migration and possibly metastasis[3][7][10]. Despite its broad signaling roles, PEA-15 is not a classical receptor, enzyme, or transporter, but rather functions as a multifunctional adapter protein integrating diverse kinase pathways.

Other names

Astrocytic phosphoprotein PEA-15PEDProliferation and apoptosis adaptor protein 15