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. Using a highly specific antiserum produced 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 cell line 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 cell supernatant 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.
Malitschek
B
B
Department of Physiological Chemistry I, Biocenter (Theodor-Boveri Institut), University of Würzburg, Germany.
Wittbrodt
J
J
Fischer
P
P
Lammers
R
R
Ullrich
A
A
Schartl
M
M
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D003532:Cyprinodontiformes; D018076:DNA, Complementary; D004789:Enzyme Activation; D029941:Fish Proteins; D005822:Genetic Vectors; D006801:Humans; D007915:Lepidoptera; D008024:Ligands; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D029941:Fish Proteins; D008024:Ligands; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D020794:Receptor Protein-Tyrosine Kinases; C077101:Xmrk protein, Xiphophorus