Gene Symbol: Ret
Description: Ret oncogene
Alias: CG1061, CG14396, D-ret, DRET, DRet, DmHD-59, DmRet, Dmel\CG14396, Dret, HD-59, MEN2, RET, Reto, dRET, dRet, dret, ret, Ret oncogene, CG14396-PA, CG14396-PB, CG14396-PC, Ret-PA, Ret-PB, Ret-PC, dret
Species: fruit fly
Products:     Ret

Top Publications

  1. Aron L, Klein P, Pham T, Kramer E, Wurst W, Klein R. Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol. 2010;8:e1000349 pubmed publisher
    ..Here, we show that aging mice lacking DJ-1 and the GDNF-receptor Ret in the DA system display an accelerated loss of SN cell bodies, but not axons, compared to mice that only lack Ret ..
  2. Sugaya R, Ishimaru S, Hosoya T, Saigo K, Emori Y. A Drosophila homolog of human proto-oncogene ret transiently expressed in embryonic neuronal precursor cells including neuroblasts and CNS cells. Mech Dev. 1994;45:139-45 pubmed
    ..for a transmembrane protein most similar in sequence to a mammalian proto-oncogene ret; thus, the gene was termed Dret. Dret mRNA is transcribed in very small amounts in the embryonic, larval, and pupal stages...
  3. Hahn M, Bishop J. Expression pattern of Drosophila ret suggests a common ancestral origin between the metamorphosis precursors in insect endoderm and the vertebrate enteric neurons. Proc Natl Acad Sci U S A. 2001;98:1053-8 pubmed
    The RET gene, encoding a receptor tyrosine kinase, is unusual among human protooncogenes in that its mutant alleles are implicated in a developmental defect involving enteric neurons as well as in tumorigenesis...
  4. Dar A, Das T, Shokat K, Cagan R. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature. 2012;486:80-4 pubmed publisher
    ..Using a Ret-kinase-driven Drosophila model of multiple endocrine neoplasia type 2 and kinome-wide drug profiling, here we ..
  5. Vidal M, Wells S, Ryan A, Cagan R. ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res. 2005;65:3538-41 pubmed
    ..associated with multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC (FMTC) have mutations in the RET proto-oncogene...
  6. Abrescia C, Sjöstrand D, Kjaer S, Ibanez C. Drosophila RET contains an active tyrosine kinase and elicits neurotrophic activities in mammalian cells. FEBS Lett. 2005;579:3789-96 pubmed
    ..Despite the absence of GDNF or GFRalpha molecules in the Drosophila genome, a RET orthologue (dRET) has recently been described in this organism and shown to be expressed in subpopulations of cells of the excretory,..
  7. Soba P, Han C, Zheng Y, Perea D, Miguel Aliaga I, Jan L, et al. The Ret receptor regulates sensory neuron dendrite growth and integrin mediated adhesion. elife. 2015;4: pubmed publisher in vivo RNAi screen in Drosophila class IV dendritic arborization (C4da) neurons and identified the conserved Ret receptor, known to play a role in axon guidance, as an important regulator of dendrite development...
  8. Kallijärvi J, Stratoulias V, Virtanen K, Hietakangas V, Heino T, Saarma M. Characterization of Drosophila GDNF receptor-like and evidence for its evolutionarily conserved interaction with neural cell adhesion molecule (NCAM)/FasII. PLoS ONE. 2012;7:e51997 pubmed publisher the central and peripheral nervous systems throughout Drosophila development, but, surprisingly, DmGfrl and DmRet expression patterns were largely non-overlapping...
  9. Tepass U, Truong K, Godt D, Ikura M, Peifer M. Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol. 2000;1:91-100 pubmed
    ..Cadherins may also contribute to neurite outgrowth and pathfinding, and to synaptic specificity and modulation in the central nervous system. ..

More Information


  1. Oates A, Wollberg P, Achen M, Wilks A. Sampling the genomic pool of protein tyrosine kinase genes using the polymerase chain reaction with genomic DNA. Biochem Biophys Res Commun. 1998;249:660-7 pubmed
    ..Furthermore, as a tool to hasten the discovery of members of gene families that are of particular interest, this method offers an opportunity to sample the genome for new members irrespective of their expression pattern. ..
  2. Hernández K, Myers L, Bowser M, Kidd T. Genetic Tools for the Analysis of Drosophila Stomatogastric Nervous System Development. PLoS ONE. 2015;10:e0128290 pubmed publisher
    ..We constructed GAL4 lines driven by fragments of the Ret promoter, which yielded expression in a subset of migrating neural SNS precursors and also included a distinct set ..
  3. Anders J, Kjar S, Ibanez C. Molecular modeling of the extracellular domain of the RET receptor tyrosine kinase reveals multiple cadherin-like domains and a calcium-binding site. J Biol Chem. 2001;276:35808-17 pubmed
    ..and binding studies, we have investigated the structural organization of the extracellular region of the RET receptor tyrosine kinase, a functional receptor for glial cell line-derived neurotrophic factor (GDNF)...
  4. Plaza Menacho I, Barnouin K, Barry R, Borg A, Orme M, Chauhan R, et al. RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements. Cell Rep. 2016;17:3319-3332 pubmed publisher
    ..Here, we show that the juxtamembrane (JM) segment enhances RET catalytic domain activity through Y687...
  5. Fung S, Wang F, Chase M, Godt D, Hartenstein V. Expression profile of the cadherin family in the developing Drosophila brain. J Comp Neurol. 2008;506:469-88 pubmed
    ..Cad87A is strongly enriched apically in epithelia and in neuronal dendrites. Fat-like, Cad86C, Cad88C, Cad89D, and Dret are expressed ubiquitously in embryonic and larval brains at low or moderate levels...
  6. Zartman J, Kanodia J, Yakoby N, Schafer X, Watson C, Schlichting K, et al. Expression patterns of cadherin genes in Drosophila oogenesis. Gene Expr Patterns. 2009;9:31-6 pubmed publisher
    ..Of particular note is the complex patterning of the region of the follicular epithelium that gives rise to the dorsal appendages, which are tubular structures that serve as respiratory organs for the developing embryo. ..
  7. Abramov Y, Kibanov M, Gvozdev V, Lavrov S. Genetic and molecular analysis of gene trans-inactivation caused by homologous eu-heterochromatic chromosome rearrangement in Drosophila melanogaster. Dokl Biochem Biophys. 2011;437:72-6 pubmed publisher
  8. Jaaro H, Beck G, Conticello S, Fainzilber M. Evolving better brains: a need for neurotrophins?. Trends Neurosci. 2001;24:79-85 pubmed
    ..Expansion of the genome projects to other invertebrates, such as molluscs and coelenterates, should provide new insights on the molecular correlates of building complex brains. ..
  9. Klein P, Müller Rischart A, Motori E, Schönbauer C, Schnorrer F, Winklhofer K, et al. Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants. EMBO J. 2014;33:341-55 pubmed publisher
    ..Glial cell line-derived neurotrophic factor (GDNF) and its signaling receptor Ret are neuroprotective in toxin-based animal models of PD...
  10. Perea D, Guiu J, Hudry B, Konstantinidou C, Milona A, Hadjieconomou D, et al. Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia. EMBO J. 2017;36:3029-3045 pubmed publisher
    Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons...
  11. Macagno J, Díaz Vera J, Yu Y, MacPherson I, Sandilands E, Palmer R, et al. FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells. PLoS Genet. 2014;10:e1004262 pubmed publisher
    ..Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway...
  12. Sopko R, Perrimon N. Receptor tyrosine kinases in Drosophila development. Cold Spring Harb Perspect Biol. 2013;5: pubmed publisher
    ..In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. ..
  13. Huen D, Elsdon M, Ponder B. The Drosophila Ret gene is transcribed in multiple alternatively spliced forms. Mol Gen Genet. 2000;264:335-40 pubmed
    We have cloned and sequenced the 5' and 3' ends of the Drosophila homolog of the vertebrate c-ret gene, Ret, and have derived from it the predicted protein sequence of Ret...
  14. Hill E, Broadbent I, Chothia C, Pettitt J. Cadherin superfamily proteins in Caenorhabditis elegans and Drosophila melanogaster. J Mol Biol. 2001;305:1011-24 pubmed
    ..Other common subclasses include the seven-helix membrane cadherins, Fat-like protocadherins and the Ret-like cadherins...
  15. Long H, Cameron S, Yu L, Rao Y. De novo GMP synthesis is required for axon guidance in Drosophila. Genetics. 2006;172:1633-42 pubmed
    ..Our study thus provides the first in vivo evidence to support an essential and specific role for de novo synthesis of guanine nucleotides in axon guidance. ..
  16. Fu S, Yang Y, Das T, Tirtha D, Yen Y, Zhou B, et al. ?-H2AX kinetics as a novel approach to high content screening for small molecule radiosensitizers. PLoS ONE. 2012;7:e38465 pubmed publisher
    ..MS0019266 and MS0017509 are promising compounds that may be candidates for further development as radiosensitizing compounds as inhibitors of ribonucleotide reductase. ..
  17. Myers L, Perera H, Alvarado M, Kidd T. The Drosophila Ret gene functions in the stomatogastric nervous system with the Maverick TGFβ ligand and the Gfrl co-receptor. Development. 2018;145: pubmed publisher
    The RET receptor tyrosine kinase is crucial for the development of the enteric nervous system (ENS), acting as a receptor for Glial cell line-derived neurotrophic factor (GDNF) via GFR co-receptors...
  18. Das T, Dana D, Paroly S, Perumal S, Singh S, Jhun H, et al. Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis. Oncogenesis. 2013;2:e69 pubmed publisher
    ..Our finding posits a novel role for Nek2 in promoting metastasis in addition to its currently defined role in promoting chromosomal instability. It provides a rationale for the selective advantage of centrosome amplification in cancer. ..
  19. Kjaer S, Kurokawa K, Perrinjaquet M, Abrescia C, Ibanez C. Self-association of the transmembrane domain of RET underlies oncogenic activation by MEN2A mutations. Oncogene. 2006;25:7086-95 pubmed
    ..endocrine neoplasia (MEN2A), mutations of cysteine residues in the extracellular juxtamembrane region of the RET receptor tyrosine kinase cause the formation of covalent receptor dimers linked by intermolecular disulfide bonds ..