Modulation of arachidonic acid metabolism by Rous sarcoma virus.
Arachidonic acid (C20:4) metabolites were released constitutively from wild-type Rous sarcoma virus-transformed chicken embryo fibroblasts (CEF). 3H-labeled C20:4 and its metabolites were released from unstimulated and uninfected CEF only in response to stimuli such as serum, phorbol ester, or the calcium ionophore A23187. High-pressure liquid chromatography analysis showed that the radioactivity released from [3H]arachidonate-labeled transformed cells was contained in free arachidonate and in the cyclooxygenase products prostaglandin E2 and prostaglandin F2 alpha; no lipoxygenase products were identified. The release of C20:4 and its metabolites from CEF infected with pp60src deletion mutants was correlated with serum-independent DNA synthesis and with the expression of the mRNA for 9E3, a gene expressed in Rous sarcoma virus-transformed cells which has homology with several mitogenic and inflammatory peptides. 3H-labeled C20:4 release was not correlated with p36 phosphorylation, which argues against a role for this protein as a phospholipase A2 inhibitor. CEF infected with other oncogenic viruses encoding a tyrosine kinase also released C20:4, as did CEF infected with viruses that contained mos and ras; however, infection with a crk-containing virus did not result in stimulation of 3H-labeled C20:4 release, suggesting that utilization of this signaling pathway is specific for particular transformation stimuli.
Barker
K
K
Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021-6399.
Aderem
A
A
Hanafusa
H
H
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D004261:DNA Replication; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D014316:Tritium
D001095:Arachidonic Acids; D012333:RNA, Messenger; D014316:Tritium; D000001:Calcimycin