Cycloheximide-induced cPLA(2) activation is via the MKP-1 down-regulation and ERK activation

Extracellular signal-regulated kinase (ERK)-dependent phosphorylation is an important regulator for cytosolic phospholipase A(2) (cPLA(2)) In this stu dy, we found that the protein synthesis inhibitor cycloheximide can potenti ate thapsigargin-induced arachidonic acid (AA) release concomitant with ERK phosphorylation from murine RAW 264.7 rmacrophages. The cycloheximide effe ct is not due to the activation of p38 mitogen-activated protein kinase (MA PK) nor c-Jun NH2-terminal kinase (JNK), because the activator of both MAPK s anisomycin does not elicit AA release. Cycloheximide effect is additive t o the tyrosine phosphatase inhibitor orthovanadate since these two stimuli induced sustained ERK activation respectively through inhibition of the tra nslation and activity of MAPK phosphatase-1 (MKP-1). (C) 2000 Elsevier Scie nce Inc. All rights reserved.