Cited by 3,738PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

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Oncogenic kinase signalling.

Blume-Jensen, Peter, Hunter, Tony·2001·Nature

DOI 10.1038/35077225

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Abstract

Protein-tyrosine kinases (PTKs) are important regulators of intracellular signal-transduction pathways mediating development and multicellular communication in metazoans. Their activity is normally tightly controlled and regulated. Perturbation of PTK signalling by mutations and other genetic alterations results in deregulated kinase activity and malignant transformation. The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its downstream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70S6K), are crucial effectors in oncogenic PTK signalling. This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity and provides an update on our knowledge about the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.

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Hallek, M. J., Danhauser-riedl, S., Herbst, R., Warmuth, M., Winkler, A., Kolb, H., Druker, B. J., Griffin, J. D., Emmerich, B., & Ullrich, A. (1996) · British Journal of Haematology · doi:10.1046/j.1365-2141.1996.6102053.x · Cited by 41
PI3 Kinase mediates transformation of hematopoietic cells by the V816 c-kit mutant
Chian, R., Young, S., Danilkovitch‐Miagkova, A., Rönnstrand, L., Leonard, E. J., Ferrao, P., Ashman, L. K., & Linnekin, D. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00562-2 · Cited by 8

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Research works printed but not linked: 3

Blume-Jensen, P. & Hunter, T. in Encyclopedia of Cancer (ed. Bertino, J. R.) (Academic, San Diego, in the press).
Blume-Jensen, P. & Hunter, T. in Cancer Research - An Encyclopedic Reference (ed. Schwab, M.) (Springer, in the press).
Blume-Jensen, P. & Hunter, T. in Encyclopedia of Cancer (ed. Bertino, J. R.) (Academic, San Diego, in the press).

Sorted by citations

The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145
Self-citation
Cell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929
EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338
Development by Self-Digestion
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,728
STATs: transcriptional control and biological impact
Levy, D. E., & Darnell, J. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm909 · Cited by 3,201

See all 3,738

Authors: Blume-Jensen, P., & Hunter, T.
Affiliations: Salk Institute for Biological Studies (US)
ORCID: Hunter, Tony
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2001-05-01
Volume: 411
Issue: 6835
Pages: 355-365
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35077225
OpenAlex: W1639582946
Cited by: 3,738
References: 93
Citations by year: 2026: 48 · 2025: 69 · 2024: 87 · 2023: 102 · 2022: 103 · 2021: 114 · 2020: 121 · 2019: 118 · 2018: 105 · 2017: 119 · 2016: 131 · 2015: 156 · 2014: 186 · 2013: 185 · 2012: 200
FWCI: 12.95
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: tyrosine kinase, oncogenic signaling, signal transduction, phosphatidylinositol 3-kinase, Akt, p70 S6 kinase, mTOR, kinase autoinhibition, malignant transformation, human malignancies
MeSH terms: Animals, Humans, Mutation, Neoplasms, Oncogenes, Protein-Tyrosine Kinases, Signal Transduction, Oncogene Proteins, Retroviridae Proteins, Oncogenic, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Receptor Protein-Tyrosine Kinases, Oncogene Protein v-akt

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