Significance Cell migration is central in physiological and pathological conditions such as immune response and cancer metastasis. The excitable network hypothesis can account for recent observations of propagating waves of signal transduction and cytoskeleton events as well as behaviors of migrating cells. However, the molecular feedback loops involved in these networks that bring about excitability are poorly understood. Here, we provide evidence for a positive-feedback loop based on a mutual inhibitory interaction between Ras and phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P 2 ]. Our results uncover an important role of PI(3,4)P 2 in the regulation of Ras activity, which may extend well beyond cell migration.
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Li et al. (2018) studied this question.
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