Off-target effects of MEK inhibitors

Eric M. Wauson, Marcy L. Guerra, Barbara Barylko, Joseph P. Albanesi, Melanie H. Cobb

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The mitogen-activated protein kinases (MAPKs) ERK1/2 regulate numerous cellular processes, including gene transcription, proliferation, and differentiation. The only known substrates of the MAP2Ks MEK1/2 are ERK1/2; thus, MEK inhibitors PD98059, U0126, and PD0325901 have been important tools in determining the functions of ERK1/2. By using these inhibitors and genetically manipulating MEK, we found that ERK1/2 activation is neither sufficient nor necessary for regulated secretion of insulin from pancreatic β cells or secretion of epinephrine from chromaffin cells. We show that both PD98059 and U0126 reduce agonist-induced entry of calcium into cells in a manner independent of their ability to inhibit ERK1/2. Caution should be used when interpreting results from experiments using these compounds.

Original languageEnglish (US)
Pages (from-to)5164-5166
Number of pages3
JournalBiochemistry
Volume52
Issue number31
DOIs
StatePublished - Aug 6 2013

ASJC Scopus subject areas

  • Biochemistry

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