The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
A Cytoplasmic Protein Stimulates Normal N- ras p21 GTPase, But Does Not Affect Oncogenic Mutants
Abstract
The role of guanine nucleotides in ras p21 function was determined by using the ability of p21 protein to induce maturation of Xenopus oocytes as a quantitative assay for biological activity. Two oncogenic mutant human N- ras p21 proteins, Asp12 and Val12, actively induced maturation, whereas normal Gly12 p21 was relatively inactive in this assay. Both mutant proteins were found to be associated with guanosine triphosphate (GTP) in vivo. In contrast, Gly12 p21 was predominantly guanosine diphosphate (GDP)-bound because of a dramatic stimulation of Gly12 p21-associated guanosine triphosphatase (GTPase) activity. A cytoplasmic protein was shown to be responsible for this increase in activity. This protein stimulated GTP hydrolysis by purified Gly12 p21 more than 200-fold in vitro, but had no effect on Asp12 or Val12 mutants. A similar factor could be detected in extracts from mammalian cells. It thus appears that, in Xenopus oocytes, this protein maintains normal p21 in a biologically inactive, GDP-bound state through its effect on GTPase activity. Furthermore, it appears that the major effect of position 12 mutations is to prevent this protein from stimulating p21 GTPase activity, thereby allowing these mutants to remain in the active GTP-bound state.
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In the citing paper
“Mutant KRAS is constitutively activated and leads to persistent downstream signaling and oncogenesis.”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [34]
In the citing paper
“Oncogenic KRAS mutations lead to decreased intrinsic GTPase activity and significantly increased resistance to GAP-mediated hydrolysis [34].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [34]
In the citing paper
“The oncogenic properties associated with KRAS G12X mutation are characterized by the deficiency of the intrinsic GTPase activity and the insensitivity for GTPase-activating proteins (GAPs) [3,4].”
In the citing paper
“In fact, every missense mutation at G12 (G12X) is oncogenic.”
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Metadata
- Authors
- Trahey, M., & McCormick, F.
- Affiliations
- Department of Molecular Biology, Cetus Corporation, Emeryville, CA 94608.
- ORCID
- McCormick, Frank
- Venue
- Science
- Published
- 1987-10-23
- Volume
- 238
- Issue
- 4826
- Pages
- 542-545
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2058511768
- Cited by
- 1,211
- References
- 23
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 19 · 2023: 12 · 2022: 12 · 2021: 19 · 2020: 14 · 2019: 9 · 2018: 17 · 2017: 18 · 2016: 20 · 2015: 17 · 2014: 10 · 2013: 9 · 2012: 18
- FWCI
- 32.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- GTPase activity, GDP-bound state, GTP hydrolysis, cytosolic proteins, guanine nucleotides
- MeSH terms
- Animals, Biological Assay, Cytoplasm, Female, Guanine Nucleotides, Guanosine Diphosphate, Guanosine Triphosphate, Guanylyl Imidodiphosphate, Hydrolysis, Immunosorbent Techniques, Mutation, Oocytes, Phosphoric Monoester Hydrolases, Proteins, Proto-Oncogene Proteins, Structure-Activity Relationship, Xenopus laevis, Proto-Oncogene Proteins p21(ras), GTP Phosphohydrolases
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