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The ortholog of the human proto-oncogene ROS1 is required for epithelial development in C. elegans.

Jones MR, Rose AM, Baillie DL - Genesis (2013)

Bottom Line: Little is known about the role of ROS1, however in vertebrates it has been implicated in promoting differentiation programs in specialized epithelial tissues.We also provide evidence of a direct relationship between ROL-3, the mucin SRAP-1, and BCC-1, the homolog of mRNA regulating protein Bicaudal-C.This study answers a longstanding question as to the developmental function of ROL-3, identifies three new genes that are expressed and function in the developing epithelium of C. elegans, and introduces the nematode as a potentially powerful model system for investigating the increasingly important, yet poorly understood, human oncogene ROS1.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. jonesmr@mail.ubc.ca

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ROL-3 has a conserved kinase domain and is structurally orthologous to the human proto-oncogene ROS1. a. Schematic showing the genomic region of C16D9.2. The position of a recombineered C-terminal GFP insertion into the fosmid WRM0633dF11, the genomic region used to drive ROL-3::GFP expression, and the deletion allele (tm3809) are show below the gene model. b. A closest neighbour tree of rol-3 derived from BlastP alignment with the putative kinase domain sequence. c. Protein schematics of C. elegans ROL-3 and Human ROS1. The positions of identified rol-3 alleles are shown. The alleles s1040ts and e754 have previously been reported (Simmer, Moorman et al. 2003). SP = Signal Peptide, Fn3 = Fibronectin type III repeat, TM = Transmembrane domain, TyrKC = Tyrosine Kinase Domain.
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fig01: ROL-3 has a conserved kinase domain and is structurally orthologous to the human proto-oncogene ROS1. a. Schematic showing the genomic region of C16D9.2. The position of a recombineered C-terminal GFP insertion into the fosmid WRM0633dF11, the genomic region used to drive ROL-3::GFP expression, and the deletion allele (tm3809) are show below the gene model. b. A closest neighbour tree of rol-3 derived from BlastP alignment with the putative kinase domain sequence. c. Protein schematics of C. elegans ROL-3 and Human ROS1. The positions of identified rol-3 alleles are shown. The alleles s1040ts and e754 have previously been reported (Simmer, Moorman et al. 2003). SP = Signal Peptide, Fn3 = Fibronectin type III repeat, TM = Transmembrane domain, TyrKC = Tyrosine Kinase Domain.

Mentions: The rol-3 locus of C. elegans encodes a type I integral membrane protein related to the sevenless subfamily of tyrosine kinase insulin receptor genes (Fig. 1b). The structure of the 2481aa protein is typical of an RTK of this class with a single transmembrane domain separating the intracellular and extracellular regions of the protein. The large extracellular portion of the protein contains an N-terminal signal peptide sequence and six fibronectin type III (Fn3) domains. The intracellular region contains a single kinase domain (TyrK; Fig. 1c). BlastP analysis identifies strong similarity between ROL-3 and the human proto-oncogene and orphan receptor ROS1 (29% similarity, 17% identity), particularly within the kinase domain (60% similarity, 35% identity), indicating that ROL-3 is the likely C. elegans ortholog of this human proto-oncogene (Acquaviva et al., 2009).


The ortholog of the human proto-oncogene ROS1 is required for epithelial development in C. elegans.

Jones MR, Rose AM, Baillie DL - Genesis (2013)

ROL-3 has a conserved kinase domain and is structurally orthologous to the human proto-oncogene ROS1. a. Schematic showing the genomic region of C16D9.2. The position of a recombineered C-terminal GFP insertion into the fosmid WRM0633dF11, the genomic region used to drive ROL-3::GFP expression, and the deletion allele (tm3809) are show below the gene model. b. A closest neighbour tree of rol-3 derived from BlastP alignment with the putative kinase domain sequence. c. Protein schematics of C. elegans ROL-3 and Human ROS1. The positions of identified rol-3 alleles are shown. The alleles s1040ts and e754 have previously been reported (Simmer, Moorman et al. 2003). SP = Signal Peptide, Fn3 = Fibronectin type III repeat, TM = Transmembrane domain, TyrKC = Tyrosine Kinase Domain.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4232869&req=5

fig01: ROL-3 has a conserved kinase domain and is structurally orthologous to the human proto-oncogene ROS1. a. Schematic showing the genomic region of C16D9.2. The position of a recombineered C-terminal GFP insertion into the fosmid WRM0633dF11, the genomic region used to drive ROL-3::GFP expression, and the deletion allele (tm3809) are show below the gene model. b. A closest neighbour tree of rol-3 derived from BlastP alignment with the putative kinase domain sequence. c. Protein schematics of C. elegans ROL-3 and Human ROS1. The positions of identified rol-3 alleles are shown. The alleles s1040ts and e754 have previously been reported (Simmer, Moorman et al. 2003). SP = Signal Peptide, Fn3 = Fibronectin type III repeat, TM = Transmembrane domain, TyrKC = Tyrosine Kinase Domain.
Mentions: The rol-3 locus of C. elegans encodes a type I integral membrane protein related to the sevenless subfamily of tyrosine kinase insulin receptor genes (Fig. 1b). The structure of the 2481aa protein is typical of an RTK of this class with a single transmembrane domain separating the intracellular and extracellular regions of the protein. The large extracellular portion of the protein contains an N-terminal signal peptide sequence and six fibronectin type III (Fn3) domains. The intracellular region contains a single kinase domain (TyrK; Fig. 1c). BlastP analysis identifies strong similarity between ROL-3 and the human proto-oncogene and orphan receptor ROS1 (29% similarity, 17% identity), particularly within the kinase domain (60% similarity, 35% identity), indicating that ROL-3 is the likely C. elegans ortholog of this human proto-oncogene (Acquaviva et al., 2009).

Bottom Line: Little is known about the role of ROS1, however in vertebrates it has been implicated in promoting differentiation programs in specialized epithelial tissues.We also provide evidence of a direct relationship between ROL-3, the mucin SRAP-1, and BCC-1, the homolog of mRNA regulating protein Bicaudal-C.This study answers a longstanding question as to the developmental function of ROL-3, identifies three new genes that are expressed and function in the developing epithelium of C. elegans, and introduces the nematode as a potentially powerful model system for investigating the increasingly important, yet poorly understood, human oncogene ROS1.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. jonesmr@mail.ubc.ca

Show MeSH
Related in: MedlinePlus