Receptor level mechanisms are required for epidermal growth factor (EGF)-stimulated extracellular signal-regulated kinase (ERK) activity pulses

Breanne Sparta, Michael Pargett, Marta Minguet, Kevin Distor, George Bell, John Albeck

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

In both physiological and cell culture systems, EGF-stimulated ERK activity occurs in discrete pulses within individual cells. Many feedback loops are present in the EGF receptor (EGFR)-ERK network, but the mechanisms driving pulsatile ERK kinetics are unknown. Here, we find that in cells that respond to EGF with frequency-modulated pulsatile ERK activity, stimulation through a heterologous TrkA receptor system results in non-pulsatile, amplitude-modulated activation of ERK. We further dissect the kinetics of pulse activity using a combination of FRET- and translocation-based reporters and find that EGFR activity is required to maintain ERK activity throughout the 10-20-minute lifetime of pulses. Together, these dataindicatethat feedbacks operating within the core Ras-Raf-MEK-ERK cascade are insufficient to drive discrete pulses of ERK activity and instead implicate mechanisms acting at the level of EGFR.

Original languageEnglish (US)
Pages (from-to)24784-24792
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number41
DOIs
StatePublished - Oct 9 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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