Drosophila RET contains an active tyrosine kinase and elicits neurotrophic activities in mammalian cells
TL;DR: Initial biochemical and functional characterization of the dRET protein in cell culture systems indicate significant conservation between the biological effects elicited by the human and Drosophila RET kinases, and suggest functions for dRET in neuronal differentiation in the fly.
About: This article is published in FEBS Letters.The article was published on 2005-07-04 and is currently open access. It has received 32 citations till now. The article focuses on the topics: Glial cell line-derived neurotrophic factor & Tyrosine phosphorylation.
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TL;DR: The ret proto-oncogene is a receptor tyrosine kinase involved in the pathogenesis of numerous severe developmental defects, particularly those in neural crest-derived structures leading to regulati...
Abstract: The ret proto-oncogene is a receptor tyrosine kinase involved in the pathogenesis of numerous severe developmental defects, particularly those in neural crest-derived structures leading to regulati...
05 Dec 2014
TL;DR: DmMANF is not required in a cell autonomous fashion for the survival and differentiation of the main cell types of the brain in the adult non-neuronal tissues and does not affect the dopaminergic system.
Abstract: REVIEW OF THE LITERATURE 1 DROSOPHILA AS A MODEL SYSTEM 1 NEUROBIOLOGY: THE STUDY OF THE NERVOUS SYSTEM 1 NEUROTROPHIC FACTORS IN VERTEBRATES AND THEIR CLASSIFICATION 2 NEUROTROPHIC FACTORS IN INVERTEBRATES 7 Drosophila Neurotrophins (DNTs) 7 Drosophila MANF (DmMANF) 8 Glia 9 Microglia –The macrophages of the vertebrate nervous system 9 IMMUNITY IN DROSOPHILA 10 Cellular immune response 11 Humoral immune response 12 Immunity in the Drosophila brain 14 AUTOPHAGY 14 OOGENESIS 15 LIN-28 AND LET-7 16 AIMS OF THE STUDY 19 MATERIALS AND METHODS 20 TABLE 1. METHODS 20 TABLE 2. FLY STRAINS 21 TABLE 3. ANTIBODIES 23 RESULTS AND DISCUSSION 24 DMMANF EXPRESSION IN THE ADULT CNS (III-IV) 24 DmMANF expression in the adult non-neuronal tissues (III) 24 DmMANF in vivo functional studies with focus to the dopaminergic system (IV)..... 25 DmMANF overexpression does not affect the dopaminergic system (IV) 25 DmMANF is not required in a cell autonomous fashion for the survival and differentiation of the main cell types of the brain (IV) 26
Cites background from "Drosophila RET contains an active t..."
...Furthermore, chimeric receptors composed from the human extracellular Ret domain and the Drosophila intracellular dRet domain, respond to human GDNF (Abrescia et al., 2005), therefore suggesting a degree of functional conservation....
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...The GDNF family ligands are secreted as pre-pro-proteins, which need to be cleaved and homodimerize in order to be functional....
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...36 EXPRESSION OF THE DROSOPHILA GDNF RECEPTOR-LIKE TRANSCRIPT IN THE ADULT BRAIN (I) ............................................................................................................................
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...Characterization of Drosophila GDNF receptor-like and evidence for its evolutionarily conserved interaction with neural cell adhesion molecule (NCAM)/FasII....
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...They signal through a heteromeric signaling complex composed of the transmembrane Trk receptor Ret and a class of co-receptor subunits [GDNF receptor (GFR) α subunits 1 to 4], which are linked to the plasma membrane by a glycosyl phosphatidylinositol (GPI) anchor (Treanor et al., 1996) (Figure 1A)....
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References
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TL;DR: The protein kinase complement of the human genome is catalogued using public and proprietary genomic, complementary DNA, and expressed sequence tag sequences to provide a starting point for comprehensive analysis of protein phosphorylation in normal and disease states and a detailed view of the current state of human genome analysis through a focus on one large gene family.
Abstract: We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons.
7,486 citations
"Drosophila RET contains an active t..." refers background in this paper
...actually correspond to pseudogenes and do not encode enzimatically active kinases [14]....
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...structural motifs which unequivocally identify RET as a unique receptor tyrosine kinase in those species [9,13,14]....
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...Fbgn0011829) is an active tyrosine kinase [14], and may therefore exert functions similar to human RET (herein hRET) with regards to downstream signaling....
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Mark Raymond Adams1, Susan E. Celniker2, Robert A. Holt1, Cheryl A. Evans1 +191 more•Institutions (23)
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.
6,180 citations
"Drosophila RET contains an active t..." refers background in this paper
...tified in the Drosophila genome [17,18,29,30], which could be taken to imply that cognate dRET ligands might be ‘‘nonneurotrophic’’ signaling factors....
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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.
Abstract: Receptor tyrosine kinases (RTKs) are cell-surface molecules that transduce signals for cell growth and differentiation. The RTK encoded by the c-ret proto-oncogene is rearranged and constitutively activated in a large proportion of thyroid papillary carcinomas, and germ-line point mutations in c-ret seem to be responsible for the dominantly inherited cancer syndromes multiple endocrine neoplasia (MEN) types 2A and B. The gene is expressed in the developing central and peripheral nervous systems (sensory, autonomic and enteric ganglia) and the excretory system (Wolffian duct and ureteric bud epithelium) of mice, indicating that it may play a role in normal development. Here we show 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. Ret is thus an essential component of a signalling pathway required for renal organogenesis and enteric neurogenesis.
1,580 citations
Howard Hughes Medical Institute1, Celera Corporation2, University of California, Berkeley3, Harvard University4, University of Pennsylvania5, Wellcome Trust6, Stanford University7, Fred Hutchinson Cancer Research Center8, National Institutes of Health9, Lawrence Berkeley National Laboratory10, University of Leeds11, University of California, San Diego12, California Institute of Technology13, Massachusetts Institute of Technology14, BC Cancer Research Centre15, University of Maryland, Baltimore16, Centre national de la recherche scientifique17, University of California, San Francisco18, Columbia University19, Baylor College of Medicine20
TL;DR: The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
Abstract: A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
1,563 citations
TL;DR: In this paper, the expression cloning and characterization of GDNFR-α, a novel glycosylphosphatidylinositol-linked cell surface receptor for glial cell line-derived neurotrophic factor (GDNF), was reported.
1,164 citations