5287
1994
eng
article
1
2011-11-25
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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
7281
1994
eng
article
1
2013-08-21
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Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene
Xmrk encodes a subclass 1 receptor tyrosine kinase (RTK) which has been cloned from the melanomainducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to ldnase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (bTGF(X), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of tbe RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating tbe significance of autocrine stimulation in RTK induced tumors in vertebrales.
8027
urn:nbn:de:bvb:20-opus-87107
In: Oncogene, 1994, 9, S. 1517-1525
Deutsches Urheberrecht
Christoph Winkler
Joachim Wittbrodt
Reiner Lammers
Axel Ullrich
Manfred Schartl
deu
swd
Japankärpfling
deu
swd
Ligand <Biochemie>
deu
swd
Tumor
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/7281/Schartl_7281.pdf
5364
1992
eng
article
1
2011-12-09
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Xmrk receptor tyrosine kinase is activated in Xiphophorus malignant melanoma
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.
urn:nbn:de:bvb:20-opus-61699
6169
In: Embo Journal (1992) , 11, 4239-4246
Deutsches Urheberrecht
Joachim Wittbrodt
Reiner Lammers
Barbara Malitschek
Axel Ullrich
Manfred Schartl
deu
swd
Physiologische Chemie
eng
uncontrolled
chimeric RTKs
eng
uncontrolled
melanoma
eng
uncontrolled
RTK
eng
uncontrolled
Xiphophorus
Chemie und zugeordnete Wissenschaften
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5364/Schartl20.pdf