title: Oncogenic K-Ras requires activation for enhanced activity.
abstract: Oncogenic Ras mutations are widely considered to be locked in a permanent 'On' state and 'constitutively active'. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.
authors: 1] Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: H
authors: H
authors: Huang
authors: 1] Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors: J
authors: J
authors: Daniluk
authors: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Y
authors: Y
authors: Liu
authors: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: J
authors: J
authors: Chu
authors: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Z
authors: Z
authors: Li
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
authors: B
authors: B
authors: Ji
authors: 1] Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: C D
authors: CD
authors: Logsdon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism
chemical_list: C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)