@article{HarthKotzschHuetal.2010,
  author    = {Harth, Stefan and Kotzsch, Alexander and Hu, Junli and Sebald, Walter and Mueller, Thomas D.},
  title     = {A Selection Fit Mechanism in BMP Receptor IA as a Possible Source for BMP Ligand-Receptor Promiscuity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68497},
  year      = {2010},
  abstract  = {Background: Members of the TGF-b superfamily are characterized by a highly promiscuous ligand-receptor interaction as is readily apparent from the numeral discrepancy of only seven type I and five type II receptors available for more than 40 ligands. Structural and functional studies have been used to address the question of how specific signals can be deduced from a limited number of receptor combinations and to unravel the molecular mechanisms underlying the protein-protein recognition that allow such limited specificity. Principal Findings: In this study we have investigated how an antigen binding antibody fragment (Fab) raised against the extracellular domain of the BMP receptor type IA (BMPR-IA) recognizes the receptor's BMP-2 binding epitope and thereby neutralizes BMP-2 receptor activation. The crystal structure of the complex of the BMPR-IA ectodomain bound to the Fab AbD1556 revealed that the contact surface of BMPR-IA overlaps extensively with the contact surface for BMP-2 interaction. Although the structural epitopes of BMPR-IA to both binding partners coincides, the structures of BMPR-IA in the two complexes differ significantly. In contrast to the structural differences, alanine-scanning mutagenesis of BMPR-IA showed that the functional determinants for binding to the antibody and BMP-2 are almost identical. Conclusions: Comparing the structures of BMPR-IA bound to BMP-2 or bound to the Fab AbD1556 with the structure of unbound BMPR-IA shows that binding of BMPR-IA to its interaction partners follows a selection fit mechanism, possibly indicating that the ligand promiscuity of BMPR-IA is inherently encoded by structural adaptability. The functional and structural analysis of the BMPR-IA binding antibody AbD1556 mimicking the BMP-2 binding epitope may thus pave the way for the design of low-molecular weight synthetic receptor binders/inhibitors.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{Schartl1988,
  author    = {Schartl, Manfred},
  title     = {A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61842},
  year      = {1988},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{RiehlSchartl1984,
  author    = {Riehl, R. and Schartl, Manfred},
  title     = {A Transmission Electron Microscopical and Freeze-Etch Study of Malignant-Melanoma in Fish},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61916},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{CavariHongFunkensteinetal.1993,
  author    = {Cavari, Benzion and Hong, Yunhan and Funkenstein, Bruria and Moav, Boaz and Schartl, Manfred},
  title     = {All-fish gene constructs for growth hormone gene transfer in fish},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61612},
  year      = {1993},
  abstract  = {In order to develop all-fish expression vectors for microinjection into fertilized fish eggs, we have prepared the following cunstructs: rainbow trout metallothionein a/b and the gilthead seabream growth hormone cDNA (ptMTa-gbsGHcDNA, ptMTb-gsbGHcDNA), carp ß-actin gilthead seabream GH cDNA (pcAßgsbGHcDNA). The inducible metallothionein promoters a and b were cloned from rainbow trout, and the constitutive promoter ß-actin was isolated from carp. The metallothionein promoters were cloned by using the PCR technique. The tMTa contains 430 bp, while the tMTb contains 260 bp (Hong et al. 1992). These two promoters were introduced to pGEM-3Z containing the GH cDNA of Sparus aurata to form ptMTa-gsbGH and ptMTb-gsbGH, respectively. The carp cytoplasmic ß-actin gene was chosen as a source for isolating strong constitutive regulatory sequences. One of these regulatory sequences in pUC118 was Iigated to GH cDNA of S. aurata to form the pcAß-gsbGHcDNA. Expression of the constructs containing the metallothionein promoters was tested in fish cell culture and was found tobe induced effectively by zinc. The ptMTa gsb-GH cDNA construct was microinjected into fertilized carp eggs, and integration in the genome of carp was detected in the DNA isolated from fins at the age of two months.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{FoernzlerWittbrodtSchartl1991,
  author    = {F{\"o}rnzler, Dorothee and Wittbrodt, Joachim and Schartl, M.anfred},
  title     = {Analysis of an esterase linked to a locus involved in the regulation of the melanoma oncogene and isolation of polymorphic marker sequences in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61726},
  year      = {1991},
  abstract  = {Melanoma formation in Xiphophorus hybrids is mediated by a growth factor receptor tyrosine kinase oncogene encoded by the Tu locus. In the wild-type parental fish no tumors occur due to the activity of a locus that regulates the activity of the melanoma oncogene. Molecu/ar identification of this regulatory locus (R) requires a precise physical map of the chromosomal region. Therefore we studied esterase isozymes in Xiphophorus, two of which have been previously reported to be linked to locus R. We confinn that ES 1 is a distant marker for R ( approx. 30cM), and contrary to earlier studies, we show that this isozyme is present in all species of the genus and at similar activity Ievels in all organs tested. ES4, which has also been reported to be linked to R, was found to be a misclassification of liver ES1. In an attempt to identify markersthat bridge the large distance between ESl and R, we have generated DNA probes which are highly polymorphic. They will be useful in finding Iandmarks on a physical map of the R-containing chromosomal region.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MalitschekWittbrodtFischeretal.1994,
  author    = {Malitschek, Barbara and Wittbrodt, Joachim and Fischer, Petra and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred},
  title     = {Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61551},
  year      = {1994},
  abstract  = {The melanoma·inducing gene of Xiphophorus fish encodes the Xmrk receptor tyrosine kinase. U sing a highly specific antiserum p~oduced against the recombinant receptor expressed with a baculovirus, it is shown that Xmrk is the most abundant phosphotyrosine protein in fish melanoma and thus highly activated in the tumors. Studies on a melanoma cellline revealed that these cells produce an activity that considerably stimulates receptor autophosphorylation. The stimulating activity induces receptor down-regulation and can be depleted from the melanoma cellsupernatant by the immobilized recombinant receptor protein. The fish melanoma cells can thus be considered autocrine tumor cells providing a source for future purification and characterization of the Xmrk ligand.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{GoetzRaulfSchartl1992,
  author    = {G{\"o}tz, Rudolf and Raulf, Friedrich and Schartl, Manfrad},
  title     = {Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61703},
  year      = {1992},
  abstract  = {Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fi.sh Xiphophorus, with the mammalian homlogues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purifi.ed recombinant BDNF. However, the activity ofrecombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng,lml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63\% and 90\% identity, respectively, indicating that NGF bad reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates ftom a common ancestral gene about 600 million years ago. By RNA gel blot anaJysis NGF mRNA was detected during late embryonie development; BDNF was present in adult brain.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlBarnekow1984,
  author    = {Schartl, Manfred and Barnekow, A.},
  title     = {Cellular src gene product detected in the freshwater sponge Spongilla lacustris},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61904},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BarnekowSchartl1987,
  author    = {Barnekow, A. and Schartl, Manfred},
  title     = {Comparative studies on the src proto-oncogene and its gene product pp60\(^{c-src}\) in normal and neoplastic tissues of lower vertebrates},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61869},
  year      = {1987},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{RiehlSchartlKollinger1984,
  author    = {Riehl, R. and Schartl, Manfred and Kollinger, G.},
  title     = {Comparative studies on the ultrastructure of malignant melanoma in fish and human by freeze-etching and transmission electron microscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61920},
  year      = {1984},
  abstract  = {Malignant melanomas (MM) in the fish Xiphophorus and in humans were studied both by transmission electron microscopy (TEM) and freeze-etching (FE). In both fish and human melanomas the cells show interdigitations of the,plasma membranes. The nuclei are large and lobulated and have many nuclear pores. Melanosomes are abundant and melanosome complexes ("compound melanosomes") occur regularly. Pinocytotic vesicles could be demonstrated in fish and human melanomas showing iocal differences in frequency and distribution patterns in the tumor. lntercellular junctions are lacking in MM cells from fish and humans. The FE technique showed considerable advantages in demonstrating membrane-surface peculiarities such as nuclear pores or pinocytotic vesicles. The FE replicas of fish melanomas are like those of humans. These findings may support the hypothesis that melanoma in fish and humans reflect the same biological phenomenon.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlBarnekowBaueretal.1982,
  author    = {Schartl, Manfred and Barnekow, A. and Bauer, H. and Anders, F.},
  title     = {Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61937},
  year      = {1982},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BirkmayerSebaldBuecher1969,
  author    = {Birkmayer, G. D. and Sebald, Walter and B{\"u}cher, Th.},
  title     = {Cytochrom-Oxydase und ein an diese assoziiertes, markiertes Protein aus 14C-markierten Mitochondrien von Neurospora crassa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82135},
  year      = {1969},
  abstract  = {no abstract available},
  subject      = {Physiologische Chemie},
  language  = {de}
}
@article{HongWinklerBremetal.1993,
  author    = {Hong, Yunhan and Winkler, Christoph and Brem, Gottfried and Schartl, Manfred},
  title     = {Development of a heavy metal-inducible fish-specific expression vector for gene transfer in vitro and in vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61666},
  year      = {1993},
  abstract  = {The promoter of the rainbow trout metallothionein B gene ( tMTb) was isolated from genomic DNA by the polymerase chain reaction (PCR ), fused to the bacterial chloramphenicol acetyltransferase (CAT) genein an expression vector, and functionally analyzed in one human cellline and four fish celllines. This promoter exhibited an extremely low basal expression in all celllines and was zincand cadmium-inducible except in the fish melanoma cell line where the promoter was completely inactive. The metal-induced expression patterns were cellline-specific. In general the fish promoter was more species- and cell type-specific than its human counterpart. In a transient assay it was functional in developing embryos of the medaka ( Oryzias /atipes). These properties make this promoter suitable for inducible, tissue-specific expression of transgenes and for in vivo studies of gene function and regulation.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MaeuelerSchartlSchartl1993,
  author    = {M{\"a}ueler, Winfried and Schartl, Angelika and Schartl, Manfred},
  title     = {Different expression patterns of oncogenes and proto-oncogenes in hereditary and carcinogen-induced tumors of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61592},
  year      = {1993},
  abstract  = {Hereditary melanoma in Xiphophorus hybrids canying the melanoma·induclng Tu-Sd locus is caused by transcriptional activation of the Xmrk gene that resides at the Tu·Sd locus and encodes a novel member of receptor tyrosine kinases (RTK). ln this study, a total of 17 hereditary melanomas from various hybrid genotypes harbouring 7 different Tu alleles were also found to aver-express the correspondlng Xmrlc alleles. The Ievei of over-expression correlated with the degree of malignancy of the melanoma. ln addition, Xsrc expression was high ln many malignant melanomas. Expression pattems and Ieveis of the Xiphophorus EGF-receptor gene (Xerb B), the c-myc (Xmyc), and the PDGF (Xsls) gene(s) were not intriguing. Transcription of the ras gene(s) may be correlated to secondary events of melanoma progression. Expression pattems of Xfms, the Xiphophorus CSF-1 receptor homologue, can be explained by different contents of infiltrating macrophages in the tumors. ln carcinogen-induced tumors includlng one melanoma no significant expression of the Xmrk oncogene could be detected. Xsrc expression, however, was strikingly high. This indicates that activation of oncogenes other than Xmrk ls instrumental in tumorigenesls of neoplasia of non-hereditary origin.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlBarnekow1984,
  author    = {Schartl, Manfred and Barnekow, A.},
  title     = {Differential expression of the cellular src gene during vertebrate development},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61893},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{NandaSchartlFeichtingeretal.1992,
  author    = {Nanda, Indrajit and Schartl, Manfred and Feichtinger, Wolfgang and Epplen, J{\"o}rg T. and Schmid, Michael},
  title     = {Early stages of sex chromosome differentiation in fish as analysed by simple repetitive DNA sequences},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61715},
  year      = {1992},
  abstract  = {Animal sex chromosome evolution has started on different occasions with a homologous pair of autosomes leading to morphologically differentiated gonosomes. In contrast to other vertebrate classes, among fishes cytologically dernonstrahle sex chromosomes are rare. In reptiles, certain motifs of simple tandemly repeated DNA sequences like (gata)\(_n\)/(gaca)\(_m\) are associated with the constitutive heterochromatin of sex chromosomes. In this study a panel of simple repetitive sequence probes was hybridized to restriction enzyme digested genomic DNA of poeciliid fishes. Apparent male heterogamety previously established by genetic experiments in Poecilia reticulata (guppy) was correlated with male-specific hybridization using the (GACA)\(_4\) probe. The (GATA)\(_4\) oligonucleotide identifies certain male guppies by a Y chromosomal polymorphism in the outbred population. In cantrast none of the genetically defined heterogametic situations in Xiphophorus could be verified consistently using the collection of simple repetitive sequence probes. Only individuals from particular populations produced sex-specific patterns of hybridization with (GATA)\(_4\). Additional poeciliid species (P. sphenops, P. velifera) harbour different sex-specifically organized simple repeat motifs. The observed sex-specific hybridization patterns were substantiated by banding analyses of the karyotypes and by in situ hybridization using the (GACA)\(_4\) probe.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlSchmidtAndersetal.1985,
  author    = {Schartl, Manfred and Schmidt, C. R. and Anders, A. and Barnekow, A.},
  title     = {Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61889},
  year      = {1985},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{RaulfRobertsonSchartl1989,
  author    = {Raulf, F. and Robertson, S. M. and Schartl, Manfred},
  title     = {Evolution of the neuron-specific alternative splicing product of the c-src proto-oncogene},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61796},
  year      = {1989},
  abstract  = {The observation of a slower migrating form of pp6oc-src in neural tissue of chicken and mouse has recently been shown to be due to an alternative transcript form of tbe c-src gene (Martinez et al.: Science 237:411-415, 1987; Levy et al.: Mol Cell Bio17:4142- 4145, 1987). An insertion of 18 basepairs between exons 3 and 4, presumed to be due to alternative splicing of a mini-exon, gives rise to six amino acid residues not found in the non-neuronal (termed flbroblastic) form of pp60\(^{c-src}\). Wehave addressed the question of the evolutionary origin of the c-src neuronal insert · and its functional signiflcance regarding neural-speciflc expression of the c-src gene. To this end we have investigated whether the c-src gene of a lower verlebrate (the teleost fish Xiphophorus) gives rise to a neural-specific transcript in an analogous manner. We could show that the fish c-src gene does encode for a "fibroblastic" and a "neuronal" form of transcript and that the neuronal transcript does indeed arise by way of alternative splicing of a mini-exon. The miniexon is also 18 basepairs long and we could demoostrate directly that this exon lies within the intron separating exons 3 and 4. For comparative purposes we have examined whether the fish c-yes gene, the member of the src gene family most closely related to c-src, also encodes a neural tissue-specific transcript. No evidence for a second transcript form in brain was obtained. This result suggests that the mini-exon arose within the c-src gene lineage sometime between the srclyes gene duplication event and the divergence of the evolutionary lineage giving rise to the teleost fish. Published genomic sequence of src-related genes in Drosophila and our own results with Hydra demoostrate no intron in these species at the analogous location, consistent with first appearance of this mini-exon sometime between 550 and 400 million years ago.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlDimitrijevicSchartl1994,
  author    = {Schartl, A. and Dimitrijevic, N. and Schartl, Manfred},
  title     = {Evolutionary origin and molecular biology of the melanoma-inducing oncogene of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61954},
  year      = {1994},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BarnekowPaulSchartl1987,
  author    = {Barnekow, A. and Paul, E. and Schartl, Manfred},
  title     = {Expression of the c-src protooncogene in human skin tumors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61870},
  year      = {1987},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}