Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP

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Title: Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP
Author: Chen, Chiyuan
Abstract: The RAF /MEK /MAP Kinase signal transduction cascade is the most extensively studied MAPK pathway that mediates diverse cellular responses to environmental cues , and makes a major contribution to Ras -dependent oncogenic transformation . The Ras effector and E3 ligase family member IMP (Impedes Mitogenic signal Propagation ) acts as a steady -state resistor within the RAFMEK - ERK kinase module . IMP concentrations are regulated by Ras , through induction of autodegradation , and can modulate signal /response thresholds by directly limiting the assembly of functional KSR1 -dependent RAF /MEK complexes . Here , we examine the mechanistic basis of signal amplitude modulation by the Ras effector IMP . We show that the capacity of IMP to inhibit signal propagation through RAF to MEK is a consequence of disrupting assembly of multivalent mitogenic complexes that are required for C -RAF kinase activation and functional coupling of active kinases to downstream substrates . We also study how Ras regulates IMP functions by isolating IMP mutants compromised for Ras interaction and how post -translational modifications such as sumoylation control IMP activities . Finally , we identify some candidate IMP binding proteins to further investigate how IMP impacts cell behaviors through protein -protein interactions and how IMP is modulated by other proteins .
URI: http : / /hdl .handle .net /2152 .5 /593
Date: 2007-08-08

Citation

Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /593 .

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