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) |
|---|---|
| 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 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Signaling threshold regulation by the Ras effector IMP. / Matheny, Sharon A.; White, Michael A.
In: Journal of Biological Chemistry, Vol. 284, No. 17, 24.04.2009, p. 11007-11011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Signaling threshold regulation by the Ras effector IMP
AU - Matheny, Sharon A.
AU - White, Michael A.
PY - 2009/4/24
Y1 - 2009/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=66449131737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66449131737&partnerID=8YFLogxK
U2 - 10.1074/jbc.R800082200
DO - 10.1074/jbc.R800082200
M3 - Article
C2 - 19091743
AN - SCOPUS:66449131737
VL - 284
SP - 11007
EP - 11011
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 17
ER -