Structure and Physiology of the RET Receptor Tyrosine Kinase
TLDR
The discovery of ret opened a field of study that has had a profound impact in cancer research, developmental biology, and neuroscience, and that continues to yield surprises and important insights to this day.Abstract:
The identification of the ret oncogene by Masahide Takahashi and Geoffrey Cooper in 1985 was both serendipitous and paradigmatic ( Takahashi et al. 1985). By transfecting total DNA from a human lymphoma into mouse NIH3T3 cells, they obtained one clone, which in secondary transformants yielded more than 100-fold improvement in transformation efficiency. Subsequent investigations revealed that the ret oncogene was not present as such in the primary lymphoma, but was derived by DNA rearrangement during transfection from normal human sequences of the ret locus. At the time, activation by DNA rearrangement had not been previously described for a transforming gene with the NIH3T3 transfection assay. The discovery of ret opened a field of study that has had a profound impact in cancer research, developmental biology, and neuroscience, and that continues to yield surprises and important insights to this day.read more
Citations
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RET revisited: expanding the oncogenic portfolio
TL;DR: The complex roles of RET in homeostasis and survival of neural lineages and in tumour-associated inflammation might also suggest potential long-term pitfalls of broadly targeting RET.
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Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor
Yujie Zhao,Alex A. Adjei +1 more
TL;DR: This comprehensive review discusses the limitations of inhibiting VEGF signaling alone as an antiangiogenic strategy, the importance of other angiogenic pathways including PDGF/PDGFR and FGF/FGFR, and the novel current and emerging agents that target multiple angiogenesis pathways for the treatment of advanced solid tumors.
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Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions
Justin F. Gainor,Alice T. Shaw +1 more
TL;DR: Patients with either ROS1 or RET rearrangements appear to have unique clinical and pathologic features that may facilitate identification and enrichment strategies, and this finding suggests that both ROS1 and RET are independent oncogenic drivers that may be viable therapeutic targets.
Journal ArticleDOI
Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence
Sales Ibiza,Bethania García-Cassani,Hélder Ribeiro,Tânia Carvalho,Luís Soares de Almeida,Rute Marques,Ana M. Misic,Casey Bartow-McKenney,Denise M. Larson,William J. Pavan,Gérard Eberl,Elizabeth A. Grice,Henrique Veiga-Fernandes +12 more
TL;DR: It is shown that ILC3 in mice sense their environment and control gut defence as part of a glial–ILC3–epithelial cell unit orchestrated by neurotrophic factors, and sheds light on a novel multi-tissue defence unit.
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A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma
TL;DR: The pathogenic, diagnostic and prognostic roles of the RET proto-oncogene in both PTC and MTC are discussed and it is suggested that the activation of RET in MTC is mainly due to activating point mutations.
References
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Journal ArticleDOI
GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons
TL;DR: In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake and did not increase total neuron or astrocyte numbers or transmitter uptake.
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Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A
Lois M. Mulligan,John B.J. Kwok,Catherine S. Healey,M J Elsdon,Charis Eng,E. Gardner,Donald R. Love,Sara E. Mole,Julie Moore,Laura Papi +9 more
TL;DR: This work has identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls, and found that 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of theRET extracellular and transmembrane domains.
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Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret
Anita Schuchardt,Vivette D. D'Agati,Lena Larsson-Blomberg,Frank Costantini,Vassilis Pachnis,Vassilis Pachnis +5 more
TL;DR: It is shown that mice homozygous for a targeted mutation in c-ret develop to term, but die soon after birth, showing renal agenesis or severe dysgenesis, and lacking enteric neurons throughout the digestive tract, indicating an essential component of a signalling pathway required for renal organogenesis and enteric neurogenesis.
Journal ArticleDOI
GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle
Christopher E. Henderson,Heidi S. Phillips,Richard A. Pollock,Alun M. Davies,Corinne Lemeulle,Mark Armanini,Lora C. Simpson,Barbara Moffet,Richard Vandlen,Vassilis E. Koliatsos,Arnon Rosenthal +10 more
TL;DR: Glial cell line-derived neurotrophic factor (GDNF), originally identified as a trophic factor specific for dopaminergic neurons, was found to be 75-fold more potent than the neurotrophins in supporting the survival of purified embryonic rat motoneurons in culture and to be a good candidate for treatment of motoneuron disease.
Journal ArticleDOI
Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC
Helen Donis-Keller,S. Dou,David Chi,Katrin M. Carlson,Koji Toshima,Terry C. Lairmore,James R. Howe,Jeffrey F. Moley,Jeffrey F. Moley,Paul J. Goodfellow,Samuel A. Wells +10 more
TL;DR: Evidence is presented that sequence changes within the coding region of the RET proto-oncogene, a putative transmembrane tyrosine kinase, may be responsible for the development of neoplasia in these inherited disorders.
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