Yuan I. ChangAlisa DamnernsawadGuangyao KongXiaona YouDemin WangJing ZhangMcArdle Laboratory for Cancer ResearchNational Yang-Ming University TaiwanMahidol UniversityBloodCenter of Wisconsin2018-12-212019-03-142018-12-212019-03-142017-10-02Small GTPases. Vol.8, No.4 (2017), 233-23621541256215412482-s2.0-84981205611https://repository.li.mahidol.ac.th/handle/123456789/41767© 2017 Taylor & Francis. Using conditional knock-in mouse models, we and others have shown that despite the very high sequence identity between Nras and Kras proteins, oncogenic Kras displays a much stronger leukemogenic activity than oncogenic Nras in vivo. In this manuscript, we will summarize our recent work of characterizing wild-type Kras function in adult hematopoiesis and in oncogenic Kras-induced leukemogenesis. We attribute the strong leukemogenic activity of oncogenic Kras to 2 unique aspects of Kras signaling. First, Kras is required in mediating cell type- and cytokine-specific ERK1/2 signaling. Second, oncogenic Kras, but not oncogenic Nras, induces hyperactivation of wild-type Ras, which significantly enhances Ras signaling in vivo. We will also discuss a possible mechanism that mediates oncogenic Kras-evoked hyperactivation of wild-type Ras and a potential approach to down-regulate oncogenic Kras signaling.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyNoteSCOPUS10.1080/21541248.2016.1215656