Activation of the Xmrk proto-oncogene of Xiphophorus by overexpression and mutational alterations. 1998

N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
Physiological Chemistry I, Theodor Boveri Institute for Biosciences (Biocenter), University of Würzburg, Germany.

Xmrk is a receptor tyrosine kinase closely related to the human EGF receptor. In the teleost fish Xiphophorus two versions of the Xmrk gene exist, an oncogene (ONC) and a proto-oncogene (INV). While ONC-Xmrk is the melanoma-inducing gene, INV-Xmrk appears not to be involved in transformation of pigment cells. To elucidate the mechanism that converts the proto-oncogene into a transforming oncogene a comparative analysis of the structure, expression and function of both versions of the gene was performed. In contrast to ONC-Xmrk which is expressed at high levels in melanoma cells, the proto-oncogene INV-Xmrk is ubiquitously expressed at very low levels indicating overexpression as one possible reason for tumorigenicity by ONC-Xmrk. As sequence comparison of the proto-oncogene and the oncogene revealed a number of amino acid changes, a possible effect of these mutations on the activation of the ONC-Xmrk receptor was determined. A constitutive activation of the oncogenic receptor was found and ectopic expression of INV-Xmrk after microinjection into medakafish embryos did not lead to the high tumour rate in transgenic fish as observed for the oncogene. Our data therefore suggest that overexpression of the receptor alone is not sufficient for melanoma induction, but that in addition activating mutations in ONC-Xmrk are responsible for its full tumorigenic potential.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009857 Oncogenes Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene. Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D011519 Proto-Oncogenes Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc. Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D003532 Cyprinodontiformes An order of fish with eight families and numerous species of both egg-laying and livebearing fish. Families include Cyprinodontidae (egg-laying KILLIFISHES;), FUNDULIDAEl; (topminnows), Goodeidae (Mexican livebearers), Jenynsiidae (jenynsiids), Poeciliidae (livebearers), Profundulidae (Middle American killifishes), Aplocheilidae, and Rivulidae (rivulines). In the family Poeciliidae, the guppy and molly belong to the genus POECILIA. Gambusia,Mosquito Fish,Platyfish,Xiphophorus,Fish, Mosquito,Gambusias
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D000090063 Proto-Oncogene Mas A protein that is encoded by the MAS1 gene. It is a receptor for ANGIOTENSIN 1-7 and acts as an antagonist of ANGIOTENSIN-2 TYPE 1 RECEPTOR. C-Mas Protein,II-Proto-Oncogene Proteins, Cellular,Mas Protein,Mas1 Protein,Proto-Oncogene Protein Mas,Proto-Oncogene Proteins C-Mas-1,C Mas Protein,C-Mas-1, Proto-Oncogene Proteins,Cellular II-Proto-Oncogene Proteins,II Proto Oncogene Proteins, Cellular,Mas, Proto-Oncogene,Protein Mas, Proto-Oncogene,Protein, C-Mas,Protein, Mas,Protein, Mas1,Proteins, Cellular II-Proto-Oncogene,Proto Oncogene Mas,Proto Oncogene Proteins C Mas 1
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA

Related Publications

N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
January 1991, Oncogene,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
December 1997, Biological chemistry,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
October 1992, Oncogene,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
August 1998, Genetics,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
November 1999, Genetics,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
June 1998, Oncogene,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
January 1989, Nucleic acids research,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
January 1985, Progress in clinical and biological research,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
November 2007, The Journal of biological chemistry,
N Dimitrijevic, and C Winkler, and C Wellbrock, and A Gómez, and J Duschl, and J Altschmied, and M Schartl
January 1997, The Journal of biological chemistry,
Copied contents to your clipboard!