4115
2010
deu
doctoralthesis
1
2010-07-19
--
2010-07-14
Die Dynamik der primären Erkennungsschritte von BMP-Rezeptoren
Dynamics of the primary recognition steps of BMP receptors
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.
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.
urn:nbn:de:bvb:20-opus-49257
4925
X123018
Deutsches Urheberrecht
Kai Heinecke
deu
swd
Knochen-Morphogenese-Proteine
deu
swd
Wirkstoff-Rezeptor-Bindung
deu
swd
Signaltransduktion
deu
uncontrolled
Signalkomplex
deu
uncontrolled
Rezeptormobilität
deu
uncontrolled
Rezeptor-Liganden-Interaktion
deu
uncontrolled
Physiologische Chemie
deu
uncontrolled
Molekulare Biophysik
deu
uncontrolled
Molekularbiologie
eng
uncontrolled
Signaling complex
eng
uncontrolled
receptor mobility
eng
uncontrolled
receptor-ligand-interaction
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/4115/DissHeinecke.pdf
5953
1994
eng
article
1
2012-06-28
--
--
Evolutionary origin and molecular biology of the melanoma-inducing oncogene of Xiphophorus
No abstract available
urn:nbn:de:bvb:20-opus-61954
6195
In: Pigment Cell Res (1994) 7, 428-32.
Deutsches Urheberrecht
A. Schartl
N. Dimitrijevic
Manfred Schartl
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5953/Schartl65.pdf
5954
1994
eng
conferenceobject
1
2012-06-28
--
--
The conservation of neurotrophic factors during vertebrate evolution
No abstract available
urn:nbn:de:bvb:20-opus-61964
6196
In: Comparative Biochemistry and Physiology / Part C: Pharmacology, Toxicology and Endocrinology (1994) 108, 1-10.
Deutsches Urheberrecht
R. Gotz
Manfred Schartl
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5954/Schartl66.pdf
5955
1994
eng
article
1
2012-06-28
--
--
Methodik und Anwendungsgebiete des genetischen Fingerabdruckverfahrens
No abstract available
urn:nbn:de:bvb:20-opus-61978
6197
In: Biologie in unserer Zeit (1994) 24, 9-14.
Deutsches Urheberrecht
T. Lubjuhn
Manfred Schartl
J. T. Epplen
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5955/Schartl68.pdf
5314
1994
eng
article
1
2011-12-01
--
--
Male polymorphism in Limia perugiae (Pisces: Poeciliidae)
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.
urn:nbn:de:bvb:20-opus-61573
6157
Behavior Genetics (1994) , 24, 95-101
Deutsches Urheberrecht
Claudia Erbelding-Denk
Johannes H. Schroder
Manfred Schartl
Indrajit Nanda
Michael Schmid
Jörg T. Epplen
deu
swd
Physiologische Chemie
eng
uncontrolled
Poeciliid fish
eng
uncontrolled
male size polymorphism
eng
uncontrolled
reproductive success
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5314/Schartl04.pdf
5315
1994
eng
article
1
2011-12-01
--
--
Sex chromosome polymorphism and heterogametic males revealed by two cloned DNA probes in the ZW/ZZ fish Leporinus elongatus
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.
urn:nbn:de:bvb:20-opus-61583
6158
In: Chromosoma (1994) , 103, 31-9
Deutsches Urheberrecht
Ichiro Nakayama
Fausto Foresti
Rita Tewari
Manfred Schartl
Daniel Chourrout
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5315/Schartl06.pdf
5286
1994
eng
article
1
2011-11-25
--
--
Neurotrophin-6 is a new member of the nerve growth factor family
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 .
urn:nbn:de:bvb:20-opus-61544
6154
Nature (1994) , 372, 266-269
Deutsches Urheberrecht
Rudolf Götz
Reinhard Köster
Christoph Winkler
Friedrich Raulf
Friedrich Lottspeich
Manfred Schartl
Hans Thoenen
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5286/Schartl01.pdf
5287
1994
eng
article
1
2011-11-25
--
--
Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand
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.
urn:nbn:de:bvb:20-opus-61551
6155
In: Journal of Biological Chemistry (1994) , 269, 14, 10423-10430
Deutsches Urheberrecht
Barbara Malitschek
Joachim Wittbrodt
Petra Fischer
Reiner Lammers
Axel Ullrich
Manfred Schartl
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5287/Schartl02.pdf
5288
1994
eng
article
1
2011-11-25
--
--
Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny
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.
urn:nbn:de:bvb:20-opus-61569
6156
Nature (1994) , 368, 539-542
Deutsches Urheberrecht
Axel Meyer
Jean M. Morrissey
Manfred Schartl
deu
swd
Physiologische Chemie
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5288/Schartl03.pdf
5336
1993
eng
article
1
2011-12-07
--
--
Sequence of the growth hormone (GH) gene from the silver carp (Hypophthalmichthys molitrix) and evolution of GH genes in vertebrates
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).
urn:nbn:de:bvb:20-opus-61620
6162
In: Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression (1993) , 1174, 285-288
Deutsches Urheberrecht
Yunhan Hong
Manfred Schartl
deu
swd
Physiologische Chemie
eng
uncontrolled
Recombinant DNA ; Growth hormone gene ; PCR; Silver carp ; Fish
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5336/Schartl10.pdf