TY - JOUR A1 - Birkmayer, G. D. A1 - Sebald, Walter A1 - Bücher, Th. T1 - Cytochrom-Oxydase und ein an diese assoziiertes, markiertes Protein aus 14C-markierten Mitochondrien von Neurospora crassa T1 - Cytochrome oxidase and associated with it a labelled protein from 14C-labelled mitochondria of Neurospora crassa N2 - no abstract available KW - Physiologische Chemie Y1 - 1969 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82135 ER - TY - JOUR A1 - Schwab, A. J. A1 - Sebald, Walter A1 - Weiss, H. T1 - Schnelle Markierung eines mitochondrial synthetisiertem Polypeptids einer Cytochromoxidasen-Präparation aus Neurospora T1 - Rapid labeling of a mitochondrially synthetized polypeptide of a cytochrome oxidase preparation from neurospora N2 - no abstracts available KW - Physiologische Chemie Y1 - 1972 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-84206 ER - TY - JOUR A1 - Sebald, Walter A1 - Weiss, H. A1 - Jackl, G. T1 - Über die Abhängigkeit des Zusammenbaus der Cytochromoxidase von der Anwesenheit der Produkte der mitochondrialen Proteinsynthese T1 - Dependence of the structure of cytochrome oxidase on the presence of products from mitochondrial protein synthesis N2 - no abstract available KW - Physiologische Chemie Y1 - 1972 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-84192 ER - TY - JOUR A1 - Jackl, G. A1 - Sebald, Walter T1 - Identification of two products of mitochondrial protein synthesis associated with oligomycin-sensitive ATPase from Neurospora crassa N2 - no abstract available KW - Physiologische Chemie Y1 - 1974 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82093 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, A. A1 - Bauer, H. A1 - Anders, F. T1 - Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61937 ER - TY - JOUR A1 - Barnekow, A. A1 - Schartl, Manfred A1 - Anders, F. A1 - Bauer, H. T1 - Identification of a fish protein associated with a kinase activity and related to the Rous sarcoma virus transforming protein N2 - No abstract available KW - Physiologische Chemie Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61946 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, A. T1 - Differential expression of the cellular src gene during vertebrate development N2 - No abstract available KW - Physiologische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61893 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, A. T1 - Cellular src gene product detected in the freshwater sponge Spongilla lacustris N2 - No abstract available KW - Physiologische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61904 ER - TY - JOUR A1 - Riehl, R. A1 - Schartl, Manfred T1 - A Transmission Electron Microscopical and Freeze-Etch Study of Malignant-Melanoma in Fish N2 - No abstract available KW - Physiologische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61916 ER - TY - JOUR A1 - Riehl, R. A1 - Schartl, Manfred A1 - Kollinger, G. T1 - Comparative studies on the ultrastructure of malignant melanoma in fish and human by freeze-etching and transmission electron microscopy N2 - 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. KW - Physiologische Chemie KW - Malignant melanoma KW - Fish KW - Human KW - Freeze-etching KW - Transmission electron microscopy Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61920 ER - TY - JOUR A1 - Schartl, Manfred A1 - Schmidt, C. R. A1 - Anders, A. A1 - Barnekow, A. T1 - Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61889 ER - TY - JOUR A1 - Maueler, W. A1 - Eigenbrodt, E. A1 - Schartl, Manfred T1 - Intermediary metabolism of normal and tumorous tissue of Xiphophorus (Teleostei: Poeciliidae) N2 - No abstract available KW - Physiologische Chemie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61855 ER - TY - JOUR A1 - Barnekow, A. A1 - Schartl, Manfred T1 - Comparative studies on the src proto-oncogene and its gene product pp60\(^{c-src}\) in normal and neoplastic tissues of lower vertebrates N2 - No abstract available KW - Physiologische Chemie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61869 ER - TY - JOUR A1 - Barnekow, A. A1 - Paul, E. A1 - Schartl, Manfred T1 - Expression of the c-src protooncogene in human skin tumors N2 - No abstract available KW - Physiologische Chemie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61870 ER - TY - JOUR A1 - Adam, D. A1 - Wittbrodt, J. A1 - Telling, A. A1 - Schartl, Manfred T1 - RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus N2 - No abstract available KW - Physiologische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61822 ER - TY - JOUR A1 - Schartl, Manfred A1 - Peter, R. U. T1 - Progressive growth of fish tumors after transplantation into thymus-aplastic (nu/nu) mice N2 - No abstract available KW - Physiologische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61833 ER - TY - JOUR A1 - Schartl, Manfred T1 - A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61842 ER - TY - JOUR A1 - Raulf, F. A1 - Robertson, S. M. A1 - Schartl, Manfred T1 - Evolution of the neuron-specific alternative splicing product of the c-src proto-oncogene N2 - 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. KW - Physiologische Chemie KW - Xiphophorus KW - teleost flsh KW - polymerase KW - chain reaction KW - RT -PCR KW - mini-exon KW - pp6oc-src Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61796 ER - TY - JOUR A1 - Wittbrodt, J. A1 - Adam, D. A1 - Malitschek, B. A1 - Maueler, W. A1 - Raulf, F. A1 - Telling, A. A1 - Robertson, M. A1 - Schartl, Manfred T1 - Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61800 ER - TY - JOUR A1 - Bernards, R. A1 - Schackleford, G. M. A1 - Gerber, M. R. A1 - Horowitz, J. M. A1 - Friend, S. H. A1 - Schartl, Manfred A1 - Bogenmann, E. A1 - Rapaport, J. M. A1 - Mcgee, T. A1 - Dryja, T. P. T1 - Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein N2 - No abstract available KW - Physiologische Chemie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61819 ER - TY - JOUR A1 - Schartl, Manfred T1 - Homology of melanoma-inducing loci in the genus Xiphophorus N2 - Several species of the genus Xiphophorus are polymorphic for specific pigment patterns. Same of these give rise to malignant melanoma following the appropriate crossings. For one of these pattern Iod from the platyfish Xiphophorus maculatus the melanoma-inducing gene has been doned and found to encode a novel receptor tyrosine kinase, designated Xmrk. Using molecular probes from this gene in Southern blot analyses on single fish DNA preparations from 600 specimens of different populations of various species of the genus Xiphophorus and their hybrids, either with or without melanomapredisposing pattern, it was shown that all individuals contain the Xmrk gene as a proto-oncogene. It is located on the sex chromosome. All fish that carry a melanoma-predisposing locus which has been identified by Mendelian genetics contain an additional copy of Xmrk, closely linked to a specific melanophore pattern locus on the sex chromosome. The melanoma-inducing loci of the different species and populations are homologous. The additional copy of Xmrk obviously arose by a geneduplication event, thereby acquiring the oncogenic potential. The homology of the melanomainducing Iod points to a similar mechanism of tumor suppression in all feral fish populations of the different species of the genus Xiphophorus. KW - Physiologische Chemie KW - Xiphophorus Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61757 ER - TY - JOUR A1 - Dracopoli, Nicholas C. A1 - Feltquate, David M. A1 - Sam, Brigitta A1 - Schartl, Manfred T1 - Taql and Mspl RFLPs are detected by the human 2,3-biphosphoglycerate mutase (BPGM) cDNA N2 - No abstract available KW - Physiologische Chemie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61763 ER - TY - JOUR A1 - Friedenreich, Hildegard A1 - Schartl, Manfred T1 - Transient expression directed by homologous and heterologous promoter and enhancer sequences in fish cells N2 - 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. KW - Physiologische Chemie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61774 ER - TY - JOUR A1 - Clauss, Gerd A1 - Winkler, Christoph A1 - Lohmeyer, Jürgen A1 - Anders, Fritz A1 - Schartl, Manfred T1 - Oncofetal antigen in Xiphophorus detected by monoclonal antibodies directed against melanoma-associated antigens N2 - 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. KW - Physiologische Chemie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61784 ER - TY - JOUR A1 - Förnzler, Dorothee A1 - Wittbrodt, Joachim A1 - Schartl, M.anfred T1 - Analysis of an esterase linked to a locus involved in the regulation of the melanoma oncogene and isolation of polymorphic marker sequences in Xiphophorus N2 - 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. KW - Physiologische Chemie KW - Xiphophorus KW - melanoma ; oncogene regulation ; esterase ; molecular marker sequences Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61726 ER - TY - JOUR A1 - Schartl, Manfred A1 - Schlupp, Ingo A1 - Schartl, Angelika A1 - Meyer, Manfred K. A1 - Nanda, Indrajit A1 - Schmid, Michael A1 - Epplen, Jörg T. A1 - Parzefall, Jakob T1 - On the stability of dispensable constituents of the eukaryotic genome: Stability of coding sequences versus truly hypervariable sequences in a clonal vertebrate, the amazon molly, Poecilia formosa N2 - In dooal unisexual vertebrales, the genes specifying the males become dispensable. To study tbe rate of such geoes the gynogeoetic all-female fisb Poecilillfonnolll was treated with androgens. Phenotypic males were obtained that exbibited the complete set of male cbaracteristics of dosely related gooocboristic species, induding body proportions, pigmentation, the extremely complex insemination apparatus of poecilüd fish, sexual bebavior, and spermatogeoesls. Tbe apparent stabllity of such genic structures, induding those involved in androgen regulation, is contrasted by high instability of noncoding sequeaces. Frequent mutations, thelr donal transmission, and at least two truly hypervariable Iod leading to individual difl'ereaces between these othenrise donal organisms were detected by DNA fingerprinting. These observations substantiate the concept that also in "ameiotic" vertebrates certain compartments of the genome are more prooe to mutatiooal alterations than others. KW - Physiologische Chemie KW - DNA fingerprinting KW - androgen-induced masculinization KW - gynogeaesls KW - simple repeat sequences Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61731 ER - TY - JOUR A1 - Winkler, Christoph A1 - Vielkind, Jürgen R. A1 - Schartl, Manfred T1 - Transient expression of foreign DNA during embryonic and larval development of the medaka fish (Oryzias latipes) N2 - Species of small fish are becoming useful tools for studies on vertebrate development. Wehave investigated the developing embryo of the Japanese medaka for its application as a transient expression system for the in vivo analysis of gene regulation and function. The temporaland spatial expression patterns ofbacterial chloramphenicol acetyltransferase and galactosidase reporter genes injected in supercoiled plasmid form into the cytoplasm of one cell of the two-cell stage embryo was promoter-specific. The transient expression was found to be mosaic within the tissue and organs reflecting the unequal distribution of extrachromosomal foreign DNA and the intensive cell mixing movements that occur in fish embryogenesis. The expression data are consistent with data on DNA fate. Foreign DNA persisted during embryogenesis and was still detectable in some 3- and 9-month-old adult fish; it was found in high molecular weight form as weil as in circular plasmid conformations. The DNA was replicated during early and late embryogenesis. Our data indicate that the developing medaka embryo is a powerful in vivo assay system for studies of gene regulation and function. KW - Physiologische Chemie KW - Medaka - Genetransfer - Transient expression - DNA fate - Fish developmental biology Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61743 ER - TY - JOUR A1 - Schartl, Manfred A1 - Adam, Dieter T1 - Molecular cloning, structural characterization, and analysis of transcription of the melanoma oncogene of xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61989 ER - TY - JOUR A1 - Schlupp, Ingo A1 - Parzefall, Jakob A1 - Epplen, Jörg T. A1 - Nanda, Indrajit A1 - Schmid, Michael A1 - Schartl, Manfred T1 - Pseudomale behaviour and spontaneous masculinization in the all-female teleost Poecilia formosa (Teleostei: Poeciliidae) N2 - Pseudosexual behaviour is a rare phenomenon associated with unisexuality in vertebrates. In the gynogenetic, all-female teleost Poecilia formosa, rare individuals occur that resemble males of closely related gonochoristic species both in behaviour and external morphology. These masculinized gynogens and normal gynogens are members of the same clone, as demonstrated by DNA-fingerprinting. The behaviour of these masculinized gynogens is described and compared to the behaviour of the gonochoristic species Poecilia mexicana, P. latipinna and their hybrid as weil as androgen-treated individuals of P. formosa. No statistically significant difTerences were found between masculinized gynogens and hormonetreated individuals nor between the gonochoristic P. mexicana and P. latipinna males. Differences exist between gonochoristic and unisexual species. Passihle causes and effects of masculinized gynogens are discussed. KW - Physiologische Chemie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61688 ER - TY - JOUR A1 - Hong, Yunhan A1 - Schartl, Manfred T1 - Structure of the rainbow trout metallothionein A gene N2 - 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. KW - Physiologische Chemie KW - Recombinant DNA ; polymerase chain reaction ; metallothionein gene ; rainbow trout ; fish Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61679 ER - TY - JOUR A1 - Wittbrodt, Joachim A1 - Lammers, Reiner A1 - Malitschek, Barbara A1 - Ullrich, Axel A1 - Schartl, Manfred T1 - Xmrk receptor tyrosine kinase is activated in Xiphophorus malignant melanoma N2 - Xmrk encodes a putative transmembrane glycoprotein of the tyrosine kinase family and is a melanoma-inducing gene in Xiphophorus. We attempted to investigate the biological function of the putative Xmrk receptor by characterizing its signalling properties. Since a potential Iigand for Xmrk has not yet been identified, it has been difficult to analyse the biochemical properlies and biological function of this cell surface protein. In an approach towards such analyses, the Xmrk extracellular domain was replaced by the closely related Iigand-binding domain sequences of the human epidennal growth factor receptor (HER) and the ligand-induced activity of the chimeric HER-Xmrk proteinwas examined. We show that the Xmrk protein is a functional receptor tyrosine kinase, is highly active in malignant melanoma and displays a constitutive autophosphorylation activity possibly due to an activating mutation in its extracellular or transmembrane domain. In the focus formation assay the HER-Xmrk chimera is a potent transfonning protein equivalent to other tyrosine kinase oncoproteins. KW - Physiologische Chemie KW - chimeric RTKs KW - melanoma KW - RTK KW - Xiphophorus Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61699 ER - TY - JOUR A1 - Götz, Rudolf A1 - Raulf, Friedrich A1 - Schartl, Manfrad T1 - Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution N2 - 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. KW - Physiologische Chemie KW - Brain-derived neurotrophic factor KW - Nerve growth factor KW - Fish KW - Recombinant protein expression KW - Neuronal survival Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61703 ER - TY - JOUR A1 - Nanda, Indrajit A1 - Schartl, Manfred A1 - Feichtinger, Wolfgang A1 - Epplen, Jörg T. A1 - Schmid, Michael T1 - Early stages of sex chromosome differentiation in fish as analysed by simple repetitive DNA sequences N2 - 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. KW - Physiologische Chemie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61715 ER - TY - JOUR A1 - Hong, Yunhan A1 - Schartl, Manfred T1 - Sequence of the growth hormone (GH) gene from the silver carp (Hypophthalmichthys molitrix) and evolution of GH genes in vertebrates N2 - 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). KW - Physiologische Chemie KW - Recombinant DNA ; Growth hormone gene ; PCR; Silver carp ; Fish Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61620 ER - TY - JOUR A1 - Adam, Dieter A1 - Dimitrijevic, Nicola A1 - Schartl, Manfred T1 - Tumor suppression in Xiphophorus by an accidentally acquired promoter N2 - 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. KW - Physiologische Chemie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61630 ER - TY - JOUR A1 - Schartl, Manfred A1 - Erbelding-Denk, Claudia A1 - Holter, Sabine A1 - Nanda, Indrajit A1 - Schmid, Michael A1 - Schroder, Johannes H. A1 - Epplen, Jörg T. T1 - Reproductive failure of dominant males in the poeciliid fish Limia perugiae determined by DNA fingerprinting N2 - Hierarchical structures among male indlviduals in a population are frequently reflected ln differences in aggressive and reproductive behavior and access to the females. In general, sodal dominance requires the Investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesls has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Borke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poecUiid fish Limia perugitu, in small matlng groups the dominant male has 8 mating success of 100%, whereas ln larger groups lts contribution to the offspring unexpectedly drops to zero. KW - Physiologische Chemie KW - reproductive success KW - sexual selection KW - size polymorpbism KW - sodal domlnance KW - simple repetitive sequences Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61643 ER - TY - JOUR A1 - Nanda, Indrajit A1 - Schartl, Manfred A1 - Epplen, Jörg T. A1 - Feichtinger, Wolfgang A1 - Schmid, Michael T1 - Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences N2 - The demonstration ofthe chromosomal mode ofsex determinationvia genetic experiments as well as the absence of heteromorphic sex chromosomes affirm poeciliid fishes as a unique group among vertebrates that are endowed with the mostprimitive form of sex chromosornes. In many different taxa the evolutionary process involved in the differentiation ofadvanced sex chromosomes is outlined through sex specifically organized repetitive sequences. In this investigation hydridization of synthetic probes specific to genomic simple repeat motifs uncovers a sex-specific hybridization pattern in certain viviparaus fishes ofthe family Poeciliidae. The hybridization pattern together with specific staining ofthe constitutive heterochromatin by C-banding reveals heterogamety in males (Poecilia reticulata) as weil as in females (P. sphenops). In P. velifera, however, C-banding alone fails to unravel the heterogametic status. The female specific W-chromosome can be detected by simple repetitive sequence probes. Therefore, the principal significance of heterochromatization as a means of generating differentiated sex chromosomes is evident. KW - Physiologische Chemie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61659 ER - TY - JOUR A1 - Hong, Yunhan A1 - Winkler, Christoph A1 - Brem, Gottfried A1 - Schartl, Manfred T1 - Development of a heavy metal-inducible fish-specific expression vector for gene transfer in vitro and in vivo N2 - 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. KW - Physiologische Chemie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61666 ER - TY - JOUR A1 - Mäueler, Winfried A1 - Schartl, Angelika A1 - Schartl, Manfred T1 - Different expression patterns of oncogenes and proto-oncogenes in hereditary and carcinogen-induced tumors of Xiphophorus N2 - 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. KW - Physiologische Chemie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61592 ER - TY - JOUR A1 - Schliewen, U. A1 - Fricke, H. A1 - Schartl, Manfred A1 - Epplen, Jörg T. A1 - Paabo, S. T1 - Which home for coelacanth? N2 - No abstract available KW - Physiologische Chemie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61606 ER - TY - JOUR A1 - Cavari, Benzion A1 - Hong, Yunhan A1 - Funkenstein, Bruria A1 - Moav, Boaz A1 - Schartl, Manfred T1 - All-fish gene constructs for growth hormone gene transfer in fish N2 - 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. KW - Physiologische Chemie KW - growth hormone gene KW - all-fish genes KW - transgenic fish KW - cellline transfection KW - Sparus aurata Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61612 ER - TY - JOUR A1 - Schartl, A. A1 - Dimitrijevic, N. A1 - Schartl, Manfred T1 - Evolutionary origin and molecular biology of the melanoma-inducing oncogene of Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61954 ER - TY - CHAP A1 - Gotz, R. A1 - Schartl, Manfred T1 - The conservation of neurotrophic factors during vertebrate evolution N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61964 ER - TY - JOUR A1 - Lubjuhn, T. A1 - Schartl, Manfred A1 - Epplen, J. T. T1 - Methodik und Anwendungsgebiete des genetischen Fingerabdruckverfahrens N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61978 ER - TY - JOUR A1 - Erbelding-Denk, Claudia A1 - Schroder, Johannes H. A1 - Schartl, Manfred A1 - Nanda, Indrajit A1 - Schmid, Michael A1 - Epplen, Jörg T. T1 - Male polymorphism in Limia perugiae (Pisces: Poeciliidae) N2 - 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. KW - Physiologische Chemie KW - Poeciliid fish KW - male size polymorphism KW - reproductive success Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61573 ER - TY - JOUR A1 - Nakayama, Ichiro A1 - Foresti, Fausto A1 - Tewari, Rita A1 - Schartl, Manfred A1 - Chourrout, Daniel T1 - Sex chromosome polymorphism and heterogametic males revealed by two cloned DNA probes in the ZW/ZZ fish Leporinus elongatus N2 - In order to study the divergence of teleost sex chromosomes, subtractive cloning was carried out between genomic DNA ofmales and females ofthe rainbow trout (XX/XY) and of Leporinus elongatus (ZW /ZZ). Inserts cloned in a plasmid vector were individually tested on Southern blots of DNA of males and females for sex specificity. No sex-specific insert was obtained from trout, but two out of ten inserts cloned from L. elongatus showed sex-specific patterns in this species: one corresponds to a sequence present on both Z and W chromosomes, while the other is W specific. Sequences of these two inserts show neither clear homology with other known sequences, nor an open reading frame. They cross-hybridize with the genomic DNA of Leporinusfriderici, but without sex-specific patterns. Twenty-four L. elongatus adults were sexed by gonadal observation, chromosomed examination and Southern hybridization with one or the other insert. Ten males and 11 females had chromosomes and hybridization patterns typical of their sex. One ZW female was recognized as a male with the W-specific probe. This was also the case for two unusual ZW males, one having a male hybridization pattern with the other probe. These three atypical individuals may result from single genetic exchanges between four regions of the Z and the W, giving rise to three atypical W chromosomes. Finding males with such atypical heterochromosomes in a female heterogametic species may indicate that a gradual transition occurs between the heterogametic systems. KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61583 ER - TY - JOUR A1 - Götz, Rudolf A1 - Köster, Reinhard A1 - Winkler, Christoph A1 - Raulf, Friedrich A1 - Lottspeich, Friedrich A1 - Schartl, Manfred A1 - Thoenen, Hans T1 - Neurotrophin-6 is a new member of the nerve growth factor family N2 - 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 . KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61544 ER - TY - JOUR A1 - Malitschek, Barbara A1 - Wittbrodt, Joachim A1 - Fischer, Petra A1 - Lammers, Reiner A1 - Ullrich, Axel A1 - Schartl, Manfred T1 - Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand N2 - 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. KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61551 ER - TY - JOUR A1 - Meyer, Axel A1 - Morrissey, Jean M. A1 - Schartl, Manfred T1 - Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny N2 - DARWIN\(^1\) believed that sexual selection accounts for the evolution of exaggerated male ornaments, such as the sword-like caudal fin extensions of male fishes of the genus Xiphophorus, that appear detrimental to survival. Swordtails continue to feature prominently in empirical work and theories of sexual selection; the pre-existing bias hypothesis has been offered as an explanation for the evolution of swords in these fishes\(^{2,3}\). Based upon a largely morphological phylogeny, this hypothesis suggests that female preference to mate with sworded males arose in ancestrally swordless species, thus pre-dating the origin of the sword itself and directly driving its evolution. Here we present a molecular phylogeny (based on mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the traditional one: it indicates that the sword originated and was lost repeatedly. Our phylogeny suggests that the ancestor of the genus is more likely to have possessed a sword than not, thus questioning the applicability of the pre-existing bias hypothesis as an explanation for the cvolution of this sexually selected trait. KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61569 ER - TY - THES A1 - Heinecke, Kai T1 - Die Dynamik der primären Erkennungsschritte von BMP-Rezeptoren T1 - Dynamics of the primary recognition steps of BMP receptors N2 - Bone Morphogenetic Proteins (BMPs) bilden zusammen mit den Activinen, Growth and Differentiation Factors (GDFs) und Transforming Growth Factor β (TGF-β) die Transforming Growth Factor β-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 nächsten Schritt wird der niederaffine Rezeptor in den Komplex rekrutiert. Bis heute sind lediglich sieben Typ-I- und fünf Typ-II-Rezeptoren bekannt, was auf eine Promiskuität in der Liganden-Rezeptor-Interaktion schließen lässt. Die Architektur beider Rezeptorsubtypen ist dabei relativ ähnlich. Beide bestehen aus einer ligandenbindenden extrazellulären Domäne, einer Transmembrandomäne sowie einer intrazellulären Kinasedomäne. Eine nacheinander ablaufende Transphosphorylierung der intrazellulären Domänen führt zu einer Phosphorylierung von SMAD-Proteinen, die dann als nachgeschaltete Vermittler fungieren und die Transkription regulierter Gene auslösen. Im Hauptteil dieser Arbeit wurden die initialen Schritte der Rezeptorkomplexformierung sowie die Mobilität der Rezeptoren mit Hilfe von fluoreszenzmikroskopischen Methoden untersucht. Dabei konnte festgestellt werden, dass für die Bildung eines Signalkomplexes eine bestimmte Schwellenkonzentration des Liganden nötig 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 Funktionalität der verschiedenen Rezeptordomänen in der Signalübermittlung, 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 Kinasedomäne abhängig 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 abhängig ist. N2 - Bone Morphogenetic Proteins (BMPs), together with Activins, Growth and Differentiation Factors (GDFs) and Transforming Growth Factor β (TGFβ), are secreted signalling proteins that belong to the Transforming Growth Factor β superfamily. They play an important role in regulating the development, maintenance and regeneration of tissues and organs. Signalling of TGFβ superfamily members occurs by binding to two types of serine-/threonine kinase receptors termed type I and type II. First, the high affinity receptor (in case of BMP2 the type I receptor) is bound, and then the low affinity receptor is recruited into the signalling complex. The fact that there are only seven type-I and five type-II receptors are known implies a limited promiscuity in ligand-receptor interaction. The architecture of both receptor subtypes is quite similar, with a small extracellular ligand-binding domain, a single transmembrane domain and an intracellular kinase domain. Subsequent transphosphorylation of the intracellular receptor domains leads to phosphorylation of SMAD proteins, which then act as downstream mediators and activate gene transcription. The main part of this work was to analyze the initial steps in receptor complex formation and the mobility of TGFβ-superfamily receptors with fluorescence microscopy techniques. It could be shown that complex formation requires a certain ligand threshold concentration and shows an all-or-nothing switch-like behaviour. Furthermore, differences between different ligands using the same receptors could be visualized. The other parts of this work deal with the functionality of the different receptor domains in signal transduction, the analysis of high- and low-affinity binding sites on whole cells and the influence of the SMAD- and MAPK-pathways on alkaline phosphatase induction. It could be shown that the type of SMAD phosphorylation ist solely dependent on the type of the kinase domain, that there exist different receptor populations on a cell that are addressed by different ligand concentrations and that alkaline phosphatase induction is highly dependent on the time course of SMAD- and MAPK-pathway activation. KW - Knochen-Morphogenese-Proteine KW - Wirkstoff-Rezeptor-Bindung KW - Signaltransduktion KW - Signalkomplex KW - Rezeptormobilität KW - Rezeptor-Liganden-Interaktion KW - Physiologische Chemie KW - Molekulare Biophysik KW - Molekularbiologie KW - Signaling complex KW - receptor mobility KW - receptor-ligand-interaction Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49257 ER -