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

23 Citations (Scopus)

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

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Mitogen-Activated Protein Kinase Kinases
Chromaffin Cells
Mitogen-Activated Protein Kinase 1
Transcription
Mitogen-Activated Protein Kinases
Epinephrine
Genes
Chemical activation
Insulin
Calcium
Substrates
Experiments
U 0126
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
PD 0325901

ASJC Scopus subject areas

  • Biochemistry

Cite this

Off-target effects of MEK inhibitors. / Wauson, Eric M.; Guerra, Marcy L.; Barylko, Barbara; Albanesi, Joseph P.; Cobb, Melanie H.

In: Biochemistry, Vol. 52, No. 31, 06.08.2013, p. 5164-5166.

Research output: Contribution to journalArticle

Wauson, Eric M. ; Guerra, Marcy L. ; Barylko, Barbara ; Albanesi, Joseph P. ; Cobb, Melanie H. / Off-target effects of MEK inhibitors. In: Biochemistry. 2013 ; Vol. 52, No. 31. pp. 5164-5166.
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