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 - Short survey
C2 - 19091743
AN - SCOPUS:66449131737
SN - 0021-9258
VL - 284
SP - 11007
EP - 11011
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 17
ER -