Signaling threshold regulation by the Ras effector IMP

Sharon A. Matheny, Michael A. White

Research output: Contribution to journalShort survey

14 Scopus citations

Abstract

The Ras effector and E3 ligase family member IMP (impedes mitogenic signal propagation) acts as a steady-state resistor within the Raf-MEK-ERK kinase module. IMP concentrations are directly regulated by Ras, through induction of autoubiquitination, to permit productive Raf-MEK complex assembly. Inhibition of Raf-MEK pathway activation by IMP occurs through the inactivation of KSR, a scaffold/adapter protein that couples activated Raf to its substrate MEK1. The capacity of IMP to inhibit signal propagation through Raf to MEK is, in part, a consequence of disrupting KSR1 homo-oligomerization and c-Raf-B-Raf hetero-oligomerization. These observations suggest that IMP functions as a threshold modulator, controlling sensitivity of the cascade to stimulus by directly limiting the assembly of functional KSR1-dependent Raf-MEK complexes.

Original languageEnglish (US)
Pages (from-to)11007-11011
Number of pages5
JournalJournal of Biological Chemistry
Volume284
Issue number17
DOIs
StatePublished - Apr 24 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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