Abstract
Signal Transduction Mutations in the small guanosine triphosphatase RAS occur in many human tumors and are thought to act by activating the mitogen-activated protein kinase (MAPK, also called ERK) signaling pathway. Gillies et al. used imaging of live single cells to measure MAPK activity in cells expressing a single wild-type or mutant isoform of human RAS. The dynamic range of the signaling pathway and its growth factor responsiveness were surprisingly unperturbed. Although RAS mutants are biochemically more active, negative feedback and other regulatory mechanisms still exert control. The oncogenic effects of RAS mutations could reflect a small increase in baseline activity of the pathway. RAS mutations may be common in cancer in part because they can be constrained and thus do not lead to cell death. Mol. Syst. Biol. 16 , e9518 (2020).
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