ArticleMolecular and cellular biology1990
Human trk oncogenes activated by point mutation, in-frame deletion, and duplication of the tyrosine kinase domain.
Article in Molecular and cellular biology, 1990. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 73 citations in OpenAlex.
- Development of PROTACs for targeted degradation of oncogenic TRK fusions.RSC chemical biology · 2026Article
- Development of PROTACs for targeted degradation of oncogenic TRK fusions.bioRxiv : the preprint server for biology · 2025Article
- Expert consensus on the diagnosis and treatment of NTRK gene fusion solid tumors in China.Thoracic cancer · 2022Article
- Review
- Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application.Journal of medicinal chemistry · 2019Article
- Comprehensive genomic profiling identifies novel NTRK fusions in neuroendocrine tumors.Oncotarget · 2018Article
- The oncogenic neurotrophin receptor tropomyosin-related kinase variant, TrkAIII.Journal of experimental & clinical cancer research : CR · 2018Review
- TRKing down an old oncogene in a new era of targeted therapy.Cancer discovery · 2015Review
- The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition.Molecular oncology · 2014Article
- Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival.The EMBO journal · 2010Article
- Article
- The dark side of the NGF family: neurotrophins in neoplasias.Brain pathology (Zurich, Switzerland) · 2006Review
- A novel mutation within the extracellular domain of TrkA causes constitutive receptor activation.Oncogene · 2001Article
- Response of cell cycle proteins to neurotrophic factor and chemokine stimulation in human neuroglia.Experimental neurology · 2001Article
- Identification and characterization of an activating TrkA deletion mutation in acute myeloid leukemia.Molecular and cellular biology · 2000Article
- TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor.Molecular and cellular biology · 2000Article
- Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000Article
- Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer.The EMBO journal · 1999Article
- Mutations in the extracellular domain cause RET loss of function by a dominant negative mechanism.Molecular and cellular biology · 1998Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant activation of the human trk proto-oncogene, a member of the tyrosine protein kinase receptor family, has been implicated in the development of certain human cancers, including colon and thyroid papillary carcinomas. trk oncogenes have also been identified in cultured cells transfected with various DNAs. In this study, we report the characterization of three in vitro-generated trk oncogenes, trk2, trk4, and trk5 (R. Oskam, F. Coulier, M. Ernst, D. Martin-Zanca, and M. Barbacid, Proc. Natl. Acad. Sci. USA 85:2964-2968, 1988), in an effort to understand the spectrum of mutational events that can activate the human trk gene. Nucleotide sequence analysis of cDNA clones of trk2 and trk4 revealed that these oncogenes were generated by a head-to-tail arrangement of two trk tyrosine protein kinase domains connected by a purine-rich region. These oncogenes code for cytoplasmic molecules of 67,000 (p67trk2) and 69,000 (p69trk4) daltons. In contrast, the product of the trk5 oncogene, gp95trk5, is a cell surface glycoprotein of 95,000 daltons. This oncogene was generated by a 153-base-pair in-frame deletion within sequences coding for the extracellular domain of the trk receptor. This activating deletion encompasses a triplet coding for one of the nine cysteine residues that the trk receptor shares with the product of the highly related trkB tyrosine protein kinase gene. Introduction of a single point mutation (TGT----AGT) in this codon resulted in a novel trk oncogene whose product, gp140S345, differs from the nontransforming trk proto-oncogene receptor in a single amino acid residue, Ser-345 instead of Cys-345. These results illustrate that multiple molecular mechanisms, including point mutation, internal deletion, and kinase domain duplication, can result in the malignant activation of the human trk proto-oncogene.
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