Identification of the expressed form of human cytosolic phospholipase A2β (cPLA2β) -: cPLA2β3 is a novel variant localized to mitochondria and early endosomes

In this study, we identify the principal splice variant of human cytosolic phospholipase A(2)beta (cPLA(2)beta) ( also known as Group IVB cPLA(2)) present in cells. In human lung, spleen, and ovary and in a lung epithelial cell line (BEAS-2B), cPLA(2)beta is expressed as a 100-kDa protein, not the 114-kDa form originally predicted. Using RNA interference, the 100-kDa protein in BEAS-2B cells was confirmed to be cPLA(2)beta. BEAS-2B cells contain three different RNA splice variants of cPLA(2)beta (beta 1, beta 2, and beta 3). cPLA(2)beta 1 is identical to the previously cloned cPLA(2)beta, predicted to encode a 114-kDa protein. However, cPLA(2)beta(2) and cPLA(2)beta 3 splice variants are smaller and contain internal deletions in the catalytic domain. The 100-kDa cPLA(2)beta in BEAS-2B cells is the translated product of cPLA(2)beta 3. cPLA(2)beta 3 exhibits calcium-dependent PLA(2) activity against palmitoylarachidonyl-phosphatidylethanolamine and low level lysophospholipase activity but no activity against phosphatidylcholine. Unlike Group IVA cPLA(2)alpha, cPLA(2)beta 3 is constitutively bound to membrane in unstimulated cells, localizing to mitochondria and early endosomes. cPLA(2)beta 3 is widely expressed in tissues, suggesting that it has a generalized function at these unique sites.