Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

The mystery of oncogenic KRAS: Lessons from studying its wild-type counter part. Small GTPases 2017 10 02;8(4):233-236

Date

07/28/2016

Pubmed ID

27449543

Pubmed Central ID

PMC5680677

DOI

10.1080/21541248.2016.1215656

Scopus ID

2-s2.0-84981205611   2 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.

Author List

Chang YI, Damnernsawad A, Kong G, You X, Wang D, Zhang J

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Genes, ras
Humans
Mutation
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75