Group IVA phospholipase A2 [cytosolic phospholipase A2a ( @entity22704 )] is a key mediator of inflammation and tumorigenesis. In this study, by using a combination of chemical inhibition and genetic approaches in @entity3392 and @entity19 cells, we identify a mechanism by which @entity22704 promotes cell proliferation. We identified 2 @entity22704 genes in @entity3392 , cpla2aa and cpla2ab, with conserved phospholipase activity. In @entity3392 , loss of @entity22704 expression or inhibition of @entity22704 activity diminished G1 progression through the cell cycle. This phenotype was also seen in both @entity19 embryonic fibroblasts and mesangial cells. G1 progression was rescued by the addition of @entity1426 or @entity1421 ( @entity1421 ), indicating a phospholipase-dependent mechanism. We further show that @entity1421 , through PI3K/AKT activation, promoted @entity69023 ( @entity69023 ) phosphorylation and @entity69023 nuclear export. This led to up-regulation of @entity69024 and down-regulation of @entity69025 ( @entity69025 ), thus promoting G1 progression. Finally, using pharmacologic inhibitors, we show that @entity22704 , rapidly accelerated @entity1492 (RAF)/MEK/ERK, and PI3K/AKT signaling pathways cooperatively regulate G1 progression in response to platelet-derived growth factor stimulation. In summary, these data indicate that @entity22704 , through its phospholipase activity, is a critical effector of G1 phase progression through the cell cycle and suggest that pharmacological targeting of this enzyme may have important therapeutic benefits in disease mechanisms that involve excessive cell proliferation, in particular, @entity703 .-Naini, S. M., Choukroun, G. J., Ryan, J. R., Hentschel, D. M., Shah, J. V., Bonventre, J. V. Cytosolic phospholipase A2a regulates G1 progression through modulating @entity69023 activity.

Cytosolic phospholipase A2a regulates G1 progression through modulating XXXX activity.

@entity69024 :: ('30222(Tax:7955)', 'Gene') :: ['cyclin D1'] @entity22704 :: ('18783(Tax:10090)', 'Gene') :: ['cpla2a', 'cPLA2a'] @entity69023 :: ('768121(Tax:7955)', 'Gene') :: ['FOXO1', 'Forkhead box protein O1'] @entity19 :: ('10090', 'Species') :: ['mouse', 'murine'] @entity1421 :: ('MESH:D015232', 'Chemical') :: ['PGE2', 'prostaglandin E2'] @entity1426 :: ('MESH:D016718', 'Chemical') :: ['arachidonic acid'] @entity1492 :: ('MESH:D005354', 'Disease') :: ['fibrosarcoma'] @entity69025 :: ('368329(Tax:7955)', 'Gene') :: ['p27', 'Kip1'] @entity3392 :: ('7955', 'Species') :: ['zebrafish'] @entity703 :: ('MESH:D007680', 'Disease') :: ['cancer and proliferative glomerulopathies']
@entity69023 :: (768121(Tax:7955),Gene) :: ['FOXO1']
