Brother’s Keeper: Wild-Type Mutant K-Ras Dimers Limit Oncogenesis Yi-Jang Lin, Kevin M. Haigis  Cell  Volume 172, Issue 4, Pages 645-647 (February 2018) DOI: 10.1016/j.cell.2018.01.019 Copyright © 2018 Elsevier Inc. Terms and Conditions

Figure 1 Alternative Models for K-Ras Signaling (A) In the dimer model, the salt bridge formed between D154 of one K-Ras molecule and R161 of a partner molecule allows for dimerization. A heterodimer between WT and mutant K-Ras would create a dimer than cannot promote the Raf-1/B-Raf heterodimer required for MAPK signaling. A homodimer between two molecules of mutant K-Ras would create a dimer than can promote MAPK signaling. The D154Q mutant would disrupt both of these dimers. (B) In this non-dimer model, D154 is required for interaction with effectors. WT (GDP-bound) K-Ras provides an anti-proliferative signal that is lost in the D154Q mutant. Moreover, K-Ras dimerization could be the by-product of effector dimerization, and D154Q would appear to disrupt dimer formation because it prevents association with the effectors (like Raf proteins) that provide the dimerization interface. Cell 2018 172, 645-647DOI: (10.1016/j.cell.2018.01.019) Copyright © 2018 Elsevier Inc. Terms and Conditions