Epidermal growth factor activates calcium channels by phospholipase A2 5-lipoxygenase-mediated leukotriene C4 production

Maikel P. Peppelenbosch*, Leon G.J. Tertoolen, Jeroen den Hertog, Siegfried W. de Laat

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

169 Citations (Scopus)

Abstract

Epidermal growth factor (EGF) induces a Ca2+ influx in many cell types, but the underlying mechanisms are so far unresolved. We report that: EGF-induced Ca2+ channel activity is eliminated by lipoxygenase inhibition and is mimicked by artificial induction of lipoxygenase activity; addition of leukotriene C4 can fully mimic EGF in its ability to activate Ca2+ channels; and EGF induces a rapid accumulation of intracellular leukotriene C4. In addition, we show that EGF-induced, Ca2+-dependent membrane hyperpolarization and junB proto-oncogene expression are dependent on lipoxygenase activity, whereas EGF-induced cytoplasmic alkalinization is not. We conclude that PLA2 5-lipoxygenase-mediated leukotriene C4 production constitutes a novel and specific signal transduction pathway in growth factor action.

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalCell
Volume69
Issue number2
DOIs
Publication statusPublished - 17 Apr 1992
Externally publishedYes

Bibliographical note

Funding Information:
search was supported by the Foundation for Biophysics (NWO). The Netherlands. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC Section 1734 solely to indicate this fact.

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