Phospholipases A2 (PLA2) hydrolyze the sn-2 ester of membrane phospholipids to release arachidonic acid, which is oxygenated to a variety of pro-inflammatory eicosanoids (prostaglandins, leukotrienes, and others). Mammalian cells contain two kinds of PLA2s involved in this process. The 87-kDa cytosolic PLA2 (c PLA2) translocates from the cytosol to internal membrane surfaces in response to an elevation of intracellular calcium. cPLA2 is also activated by phosphorylation. We propose to study the molecular basis of the selective targeting of c PLA2 to intracellular membranes and to study its regulation by phosphorylation in keratinocytes. Mammalian secreted PLA2s (sPLA2) are released from cells by the classical and regulated secretory pathways. After release, the humar group IIA sPLA2 binds to cell surface heparan sulfate and then becomes shuttled into intracellular about membrane compartments. Studies are proposed to determine the cellular site of arachidonate release by this sPLA2. These studies will contribute to our understanding of the regulation of eicosanoid production in mammalian cells.
| Okeley, Nicole M; Gelb, Michael H (2004) A designed probe for acidic phospholipids reveals the unique enriched anionic character of the cytosolic face of the mammalian plasma membrane. J Biol Chem 279:21833-40 |
