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.”
Citations
Cites
G proteins and dual control of adenylate cyclase
Gilman, A. G. (1984) · Cell · doi:10.1016/0092-8674(84)90336-2 · Cited by 1,772
Furth, M. E., Davis, L. J., Fleurdelys, B. E., & Scolnick, E. M. (1982) · Journal of Virology · doi:10.1128/jvi.43.1.294-304.1982 · Cited by 800
Comparative biochemical properties of normal and activated human ras p21 protein
McGrath, J. P., Capon, D. J., Goeddel, D. V., & Levinson, A. D. (1984) · Nature · doi:10.1038/310644a0 · Cited by 699
JURNAK, F. A. (1985) · Science · doi:10.1126/science.3898365 · Cited by 621
Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules.
Gibbs, W. W., Sigal, I. S., Poe, M., & Scolnick, E. M. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.18.5704 · Cited by 580
Biological and biochemical properties of human rasH genes mutated at codon 61
Der, C. J., Finkel, T., & Cooper, G. M. (1986) · Cell · doi:10.1016/0092-8674(86)90495-2 · Cited by 536
The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity
Sweet, R. W., Yokoyama, S., Kamata, T., Feramisco, J. R., Rosenberg, M. J., & Gross, M. S. (1984) · Nature · doi:10.1038/311273a0 · Cited by 532
RAS proteins can induce meiosis in xenopus oocytes
Birchmeier, C., Broek, D., & Wigler, M. H. (1985) · Cell · doi:10.1016/0092-8674(85)90233-8 · Cited by 342
Changes in protein phosphorylation accompanying maturation of Xenopus laevis oocytes
Maller, J. L., Wu, M. W., & Gerhart, J. C. (1977) · Developmental Biology · doi:10.1016/0012-1606(77)90093-8 · Cited by 276
Wu, M., & Gerhart, J. C. (1980) · Developmental Biology · doi:10.1016/0012-1606(80)90131-1 · Cited by 245
A Model for the Tertiary Structure of p21, the Product of the ras Oncogene
McCormick, F. P., Clark, B. F. C., la Cour, T. F. M., Kjeldgaard, M., Nørskov‐Lauritsen, L., & Nyborg, J. (1985) · Science · doi:10.1126/science.3898366 · Cited by 245
Self-citationManne, V., Bekesi, E., & Kung, H. F. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.2.376 · Cited by 177
Gordon, J. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63613-0 · Cited by 146
Ras p21 proteins with high or low GTPase activity can efficiently transform NIH3T3 cells
Lacal, J. C., Srivastava, S. K., Anderson, P. S., & Aaronson, S. A. (1986) · Cell · doi:10.1016/0092-8674(86)90270-9 · Cited by 111
Purification and Characterization of Human H-ras Proteins Expressed in Escherichia coli
Gross, M. S., Sweet, R. W., Sathe, G. M., Yokoyama, S., Fasano, O., Goldfarb, M. P., Wigler, M. H., & Rosenberg, M. J. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.5.1015-1024.1985 · Cited by 105
Biochemical and biological properties of the human N-ras p21 protein.
Trahey, M., Milley, R. J., Cole, G. E., Innis, M. A., Paterson, H., Marshall, C. J., Hall, A., & McCormick, F. P. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.1.541 · Cited by 105
Self-citationMerriam, R. W. (1971) · Experimental Cell Research · doi:10.1016/0014-4827(71)90588-x · Cited by 82
LaMarca, M. J., Smith, L. D., & Strobel, M. C. (1973) · Developmental Biology · doi:10.1016/0012-1606(73)90342-4 · Cited by 78
Viral Harvey ras p21 expressed in Escherichia coli purifies as a binary one-to-one complex with GDP.
Poe, M., Scolnick, E. M., & Stein, R. B. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89207-9 · Cited by 66
Manne, V., Yamazaki, S., & Kung, H. F. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.22.6953 · Cited by 66
Biochemical characterization of polypeptides encoded by mutated human Ha-ras1 genes.
Colby, W. W., Hayflick, J. S., Clark, S. G., & Levinson, A. D. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.730 · Cited by 42
Wong, G. A., Arnheim, N., Clark, R., McCabe, P. C., Innis, M. A., Aldwin, L. A., Nitecki, D. E., & McCormick, F. P. (1986) · PubMed · Cited by 39
Self-citationGUANINE NUCLEOTIDE BINDING ACTIVITY OF THE SRC GENE PRODUCT OF RAT‐DERIVED MURINE SARCOMA VIRUSES
Scolnick, E. M., Shih, T. Y., Maryak, J. M., Ellis, R. J., Chang, E. H., & Lowy†, D. (1980) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1980.tb27981.x · Cited by 9
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Research works printed but not linked: 2
- Gibbs, J. B., Proceedings of the National Academy of Sciences of the United States of America 81: 5704 (1984).
- Manne, V., Proceedings of the National Academy of Sciences of the United States of America 81: 6953 (1984).
Cited by
Sorted by citations
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557
Takai, Y., Sasaki, T., & Matozaki, T. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.153 · Cited by 2,511
The GTPase superfamily: a conserved switch for diverse cell functions
Bourne, H. R., Sanders, D. A. R., & McCormick, F. P. (1990) · Nature · doi:10.1038/348125a0 · Cited by 2,336
Self-citationRAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943
Self-citationPhosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
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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