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Cited by 85Protein Kinase Regulation and GTPase SignalingDevelopmental Biology and Gene RegulationProtein Tyrosine Phosphatases

Developmentally-regulated expression of murine K-ras isoforms

Pells, S, Divjak, M, Romanowski, P, Impey, H, Hawkins, N J, Clarke, A R, Hooper, M L, Williamson, D J·1997·Oncogene
DOI 10.1038/sj.onc.1201354
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Abstract

The products (p21) of the three mammalian H-, N- and K-ras genes play important roles in intracellular signal transduction, linking membrane receptor kinases to the nuclear pathway through raf and mitogen activated protein kinase. They are involved in the regulation of proliferation and differentiation, and activating mutations of these genes are commonly associated with human cancers. Two p21 proteins are encoded by the K-ras gene (p21K-rasA and p21K-rasB) due to alternative splicing of the last exon. While the four p21ras proteins are highly homologous, their sequences diverge significantly at the C-termini, to which distinct biochemical and perhaps even functional differences may be ascribed. However, H-, N- and K-rasB appear to be ubiquitously expressed, with little evidence of tissue-specific or developmental regulation. In contrast, we now demonstrate that the expression of K-rasA is strikingly different. K-rasA is induced during differentiation of pluripotent embryonal stem cells in vitro. Its expression during early embryogenesis is limited temporally and spatially in a tissue-specific distribution which is largely maintained as an adult. This suggests a distinct biological role for p21K-rasA.

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  • Activated KRAS is associated with tumorigenesis, aggressive disease, and poor prognosis.

    “The activated state of KRAS accumulating in vivo results in the activation of downstream signaling pathways and is associated with tumorigenesis, aggressive disease, and poor prognosis [14, 15].”

    From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [14]

  • The activated state of KRAS accumulating in vivo results in activation of downstream signaling pathways.

    “The activated state of KRAS accumulating in vivo results in the activation of downstream signaling pathways and is associated with tumorigenesis, aggressive disease, and poor prognosis [14, 15].”

    From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [14]

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Authors
Pells, S., Divjak, M., Romanowski, P., Impey, H., Hawkins, N. J., Clarke, A. R., Hooper, M. L., & Williamson, D. J.
Affiliations
  • University of Edinburgh (GB)
  • St Vincent's Hospital Sydney (AU)
  • UNSW Sydney (AU)
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
1997-10-09
Volume
15
Issue
15
Pages
1781-1786
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1201354
OpenAlex
W2314235576
Cited by
83
References
1
Citations by year
2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 4
FWCI
0.83
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Sussex
  • University of Edinburgh
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 › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
KRAS, alternative splicing, developmental regulation, embryonic development, tissue-specific gene expression, p21ras, signal transduction, Raf, mitogen-activated protein kinase, cell proliferation and differentiation
MeSH terms
Animals, Cell Differentiation, Humans, Mice, Inbred BALB C, Genes, ras, RNA, Messenger, Alternative Splicing, Gene Expression Regulation, Developmental, Mice

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