IMP impedes Ras mitogenic signaling by limiting KSR1 complexes

IMP impedes Ras mitogenic signaling by limiting KSR1 complexes. In the absence of mitogen, IMP blocks KSR1 C-terminal homo-oligomerization (Step 1), KSR1-c-Raf binding (Step 2), B-Raf-MEK binding without affecting their association with KSR1 (Step 3), and B-Raf-c-Raf hetero-oligomerization (Step 4). Upon stimulation, Ras-GTP binds IMP and activates its autoubiquitination, thus relieving signal inhibition. Concomitantly, Ras-GTP activates Raf and allows subsequent KSR1 complex formation and ERK pathway signaling.

Publication

Signaling Threshold Regulation by the Ras Effector IMP. (2009) Sharon A. Matheny, et al. J Biol Chem. 2009 Apr 24;284(17):11007-11011. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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