@article{AdamWittbrodtTellingetal.1988, author = {Adam, D. and Wittbrodt, J. and Telling, A. and Schartl, Manfred}, title = {RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61822}, year = {1988}, abstract = {No abstract available}, subject = {Physiologische Chemie}, language = {en} } @article{AdamDimitrijevicSchartl1993, author = {Adam, Dieter and Dimitrijevic, Nicola and Schartl, Manfred}, title = {Tumor suppression in Xiphophorus by an accidentally acquired promoter}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61630}, year = {1993}, abstract = {Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is. suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologaus recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.}, 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} } @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{BarnekowSchartlAndersetal.1982, author = {Barnekow, A. and Schartl, Manfred and Anders, F. and Bauer, H.}, title = {Identification of a fish protein associated with a kinase activity and related to the Rous sarcoma virus transforming protein}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61946}, year = {1982}, abstract = {No abstract available}, subject = {Physiologische Chemie}, language = {en} } @article{BernardsSchacklefordGerberetal.1989, author = {Bernards, R. and Schackleford, G. M. and Gerber, M. R. and Horowitz, J. M. and Friend, S. H. and Schartl, Manfred and Bogenmann, E. and Rapaport, J. M. and Mcgee, T. and Dryja, T. P.}, title = {Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61819}, year = {1989}, 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{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{ClaussWinklerLohmeyeretal.1990, author = {Clauss, Gerd and Winkler, Christoph and Lohmeyer, J{\"u}rgen and Anders, Fritz and Schartl, Manfred}, title = {Oncofetal antigen in Xiphophorus detected by monoclonal antibodies directed against melanoma-associated antigens}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61784}, year = {1990}, abstract = {Monoclonal antlbodies (MAbs) directed against Xiphophorus melanoma cells were deve(oped and tested by lndirect immunofluorescence and Immunoperoxidase staining for reactivity with a panel of I 5 allogeneic tissues and 12 allogeneic cell llnes. The reactivity of such MAbs was restricted to melanoma cells from tumor biopsies and melanoma-derived cell lines. ln addition, all embryonie cells of all histiotypes from developmental stages later than mld·organogenesis and from corresponding short term in vitro cultures reacted with these MAbs. ln contrast, normal tissues and organs from adult fish dlsplayed no reactivity, thus implying that the melanoma-associated antigens detected by the MAbs described are oncofetal antigens.}, subject = {Physiologische Chemie}, language = {en} } @article{DracopoliFeltquateSametal.1990, author = {Dracopoli, Nicholas C. and Feltquate, David M. and Sam, Brigitta and Schartl, Manfred}, title = {Taql and Mspl RFLPs are detected by the human 2,3-biphosphoglycerate mutase (BPGM) cDNA}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61763}, year = {1990}, abstract = {No abstract available}, subject = {Physiologische Chemie}, language = {en} } @article{ErbeldingDenkSchroderSchartletal.1994, author = {Erbelding-Denk, Claudia and Schroder, Johannes H. and Schartl, Manfred and Nanda, Indrajit and Schmid, Michael and Epplen, J{\"o}rg T.}, title = {Male polymorphism in Limia perugiae (Pisces: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61573}, year = {1994}, abstract = {The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispafiola, consists of three male size morphs with uniform females. Large males differentiate at a size va:rying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, !arge males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all malemorphs can switch from courtship display to sneak-chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant a-males as weil as small subordinate \(\delta\)-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intemediate subordinate ß- and \(\gamma\)-males. Breeding experiments with the three male morphs can best be explained by a model of Y -linked genes for small and !arge size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for !arge or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor.}, subject = {Physiologische Chemie}, language = {en} } @article{FriedenreichSchartl1990, author = {Friedenreich, Hildegard and Schartl, Manfred}, title = {Transient expression directed by homologous and heterologous promoter and enhancer sequences in fish cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61774}, year = {1990}, abstract = {ln order to construct fish specific expression vectors for studies on gene regulation in vitro and in vivo a variety of heterologous enhancers and promoters from mammals and from viruses of higher vertebrate cells were tested for expression of the bacterial chloramphenicol acetyl transferase reporter gene in three teleost fish cell lines. Several viral enhancers were found to be constitutively active at high Ieveis. The human metallothionein promoter showed inducible expression in the presence of heavy metal Ions. A fish sequence was isolated that can be used as a homologous constitutively active promoter for expression of foreign genes. Using the human growth hormone gene with an active promoter in fish cells for transient expression insufficient splicing and Iack of translation were observed, pointing to limitations in the use of heterologous genes in gene transfer experiments. On the contrary, some heterologous promoters and enhancers functioned in fish c as weil as in their cell type of origin, indicating t at corresponding transcription factors are sufficient conserved between fish and human over a period of 900 million years of Independent evolution.}, 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} } @inproceedings{GotzSchartl1994, author = {Gotz, R. and Schartl, Manfred}, title = {The conservation of neurotrophic factors during vertebrate evolution}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61964}, year = {1994}, abstract = {No abstract available}, subject = {Physiologische Chemie}, language = {en} } @article{GoetzKoesterWinkleretal.1994, author = {G{\"o}tz, Rudolf and K{\"o}ster, Reinhard and Winkler, Christoph and Raulf, Friedrich and Lottspeich, Friedrich and Schartl, Manfred and Thoenen, Hans}, title = {Neurotrophin-6 is a new member of the nerve growth factor family}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61544}, year = {1994}, abstract = {DURING vertebrale development, many neurons depend for survival and differentiation on their target cells\(^{1-3}\). The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF)\(^1\). NGF and the other known members of tbe neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT -3) and neurotrophin-4/5 (NT -4/5) are conserved as distinct genes over large evolutionary distances\(^{4 -6}\). Here we report the cloning of neurotrophin-6 (NT -6), a new member of this family from the teleost fish Xiphophorus. NT -6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT -6 from cell surface and extracellular matrix molecules. Recombinant purified NT -6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency. NT -6 is expressed in tbe embryonie valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding molecuJes may modulate its action in the nervous system .}, 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} } @phdthesis{Heinecke2010, author = {Heinecke, Kai}, title = {Die Dynamik der prim{\"a}ren Erkennungsschritte von BMP-Rezeptoren}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-49257}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Bone Morphogenetic Proteins (BMPs) bilden zusammen mit den Activinen, Growth and Differentiation Factors (GDFs) und Transforming Growth Factor \&\#946; (TGF-\&\#946;) die Transforming Growth Factor \&\#946;-Superfamilie von sekretierten Signalproteinen. Sie spielen eine wichtige Rolle in der Entwicklung, Erhaltung und Regeneration von Geweben und Organen. Die Signalvermittlung dieser Proteine erfolgt durch die Bindung von zwei verschiedenen Typen von Serin-/Threonin-Kinaserezeptoren, die als Typ-I- und Typ-II-Rezeptoren bezeichnet werden. Im ersten Schritt erfolgt die Bindung an den hochaffinen Rezeptor (im Fall von BMP-2 der Typ-I-Rezeptor), im n{\"a}chsten Schritt wird der niederaffine Rezeptor in den Komplex rekrutiert. Bis heute sind lediglich sieben Typ-I- und f{\"u}nf Typ-II-Rezeptoren bekannt, was auf eine Promiskuit{\"a}t in der Liganden-Rezeptor-Interaktion schließen l{\"a}sst. Die Architektur beider Rezeptorsubtypen ist dabei relativ {\"a}hnlich. Beide bestehen aus einer ligandenbindenden extrazellul{\"a}ren Dom{\"a}ne, einer Transmembrandom{\"a}ne sowie einer intrazellul{\"a}ren Kinasedom{\"a}ne. Eine nacheinander ablaufende Transphosphorylierung der intrazellul{\"a}ren Dom{\"a}nen f{\"u}hrt zu einer Phosphorylierung von SMAD-Proteinen, die dann als nachgeschaltete Vermittler fungieren und die Transkription regulierter Gene ausl{\"o}sen. Im Hauptteil dieser Arbeit wurden die initialen Schritte der Rezeptorkomplexformierung sowie die Mobilit{\"a}t der Rezeptoren mit Hilfe von fluoreszenzmikroskopischen Methoden untersucht. Dabei konnte festgestellt werden, dass f{\"u}r die Bildung eines Signalkomplexes eine bestimmte Schwellenkonzentration des Liganden n{\"o}tig ist und dass der Mechanismus nach einem Alles-oder-Nichts-Prinzip wie ein Schalter funktioniert. Außerdem konnten Unterschiede in der Nutzung der gleichen Rezeptoren durch verschiedene Liganden festgestellt werden. Die anderen Teile der Arbeit befassen sich mit der Funktionalit{\"a}t der verschiedenen Rezeptordom{\"a}nen in der Signal{\"u}bermittlung, der Analyse von hoch- und niederaffinen Ligandenbindestellen auf ganzen Zellen sowie dem Einfluss des SMAD- und des MAPK-Signalwegs auf die Induktion der Alkalischen Phosphatase. Dabei konnte gezeigt werden, dass die Art der SMAD-Phosphorylierung allein vom Typ der Kinasedom{\"a}ne abh{\"a}ngig ist, dass auf einer Zelle verschiedene Rezeptorpopulationen existieren, welche von unterschiedlichen Ligandenkonzentrationen angesprochen werden, und dass die Induktion der Alkalischen Phosphatase stark vom zeitlichen Verlauf der SMAD- und MAPK-Aktivierung abh{\"a}ngig ist.}, subject = {Knochen-Morphogenese-Proteine}, language = {de} } @article{HongSchartl1993, author = {Hong, Yunhan and Schartl, Manfred}, title = {Sequence of the growth hormone (GH) gene from the silver carp (Hypophthalmichthys molitrix) and evolution of GH genes in vertebrates}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61620}, year = {1993}, abstract = {The silver carp (Hypophthalmichthys molitrix) growth hormone (GH) genewas isolated and sequenced following amplification from genomic DNA by the polymerase chain reaction. The gene spans a region of approx. 2.5 kb nucleotides (nt) and consists of five exons. The sequence predicts a polypeptide of 210 amino acids (aa) including a putative signal peptide of 22 hydrophobic aa residues. The arrangement of exons and introns is identical to the GH genes of common carp, grass carp, and very similar to mammals and birds, but quite different from that for the GH genes of tilapia and salmonids. The silver carp GH gene shares a high homology at the nt and aa Ievels with those of grass carp (95.3\% nt, 99.5\% aa) and of common carp (81\% nt, 95.7\% aa).}, subject = {Physiologische Chemie}, language = {en} } @article{HongSchartl1992, author = {Hong, Yunhan and Schartl, Manfred}, title = {Structure of the rainbow trout metallothionein A gene}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61679}, year = {1992}, abstract = {To investigate the regulation of metallothionein-encoding genes in fish, we have isolated and sequenced the rainbow trout metallothionein-A-encoding gene (tMT-A) by polymerase chain reaction. This gene spans about 1.1 kb, consists of three exons and two introns, and has an A+ T-rieb 5' -region which contains a TATAAA signal, and two metal responsive elements (MREs). The transcription start point is centered around an A residue 81 nt upstream of the ATG codon.}, subject = {Physiologische Chemie}, language = {en} } @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} }