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 language | English (US) |
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Pages (from-to) | 11007-11011 |
Number of pages | 5 |
Journal | Journal of Biological Chemistry |
Volume | 284 |
Issue number | 17 |
DOIs | |
State | Published - Apr 24 2009 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology