The mystery of oncogenic KRAS: Lessons from studying its wild-type counter part

Yuan I. Chang, Alisa Damnernsawad, Guangyao Kong, Xiaona You, Demin Wang, Jing Zhang*

*Corresponding author for this work

Research output: Contribution to journalComment/debate

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)233-236
Number of pages4
JournalSmall GTPases
Volume8
Issue number4
DOIs
StatePublished - 2 Oct 2017

Keywords

  • leukemogenesis
  • oncogenic Kras
  • oncogenic Nras
  • SOS1
  • wild-type Kras

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