Lipocortin 1 and the control of cPLA2 activity in A549 cells. Glucocorticoids block EGF stimulation of cPLA2 phosphorylation.
Epidermal growth factor (EGF) rapidly stimulates the release of arachidonic acid in A549 cells by a mechanism that is sensitive to pertussis toxin [1]. We show that EGF treatment of A549 cells stimulates phosphorylation of cytosolic phospholipase A2 (cPLA2) through a mechanism that is similarly inhibited by pertussis toxin. The level of cPLA2 expression is, apparently, not changed during this period. Pretreatment of cells with dexamethasone (10-100 nM) for 3 hr prevents this activation of cPLA2 by EFG, without changing the level of cPLA21 expression. The effect of dexamethasone is reversed in the presence of the neutralizing antilipocortin Mab 1A but not by the nonneutralizing antilipocortin 1 control Mab 1B. This strongly suggests that lipocortin 1 mediates the effect of dexamethasone by inhibiting activation of cPLA2. This concept is supported by the fact that a peptide Lc13-25 (10-200 micrograms/mL), derived from the N-terminus of lipocortin 1, also inhibits activation of cPLA2 by EGF in these cells.
Croxtall
J D
JD
Department of Biochemical Pharmocology, William Harvey Research Insititute, Medical College of St. Bartholomews Hospital, London, UK.
Choudhury
Q
Q
Newman
S
S
Flower
R J
RJ
D000230:Adenocarcinoma; D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054467:Phospholipases A2
D017305:Annexin A1; D005938:Glucocorticoids; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins