Epidermal growth factor-induced actin remodeling is regulated by 5-lipoxygenase and cyclooxygenase products.
In a number of cell types, epidermal growth factor (EGF) evokes dramatic morphological changes, cortical actin polymerization, and stress fiber breakdown. The molecular processes by which increased EGF receptor tyrosine kinase activity results in actin reorganization and morphological changes are unresolved. Recently, we demonstrated that arachidonic acid metabolites function in EGF signal transduction. We now report that in A431 cells, HeLa cells, and rat-1 fibroblasts, the EGF-induced cortical actin polymerization is produced by lipoxygenase metabolism, whereas in these cells stress fiber breakdown is mediated by cyclooxygenase metabolites. Also, the EGF-provoked rounding up in A431 cells is dependent on arachidonic acid metabolism. We conclude that leukotrienes and prostaglandins act in concert, as second messengers, to produce morphological effects and actin reorganization, providing a novel mechanism for directing growth factor-induced cytoskeletal changes.
Peppelenbosch
M P
MP
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Tertoolen
L G
LG
Hage
W J
WJ
de Laat
S W
SW
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D015289:Leukotrienes / Q000494:pharmacology; D046911:Macromolecular Substances; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000199:Actins; D015289:Leukotrienes; D046911:Macromolecular Substances; D011453:Prostaglandins; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors