Signal Transduction by the Oncogenic Receptor Tyrosine Kinase Xmrk in Melanoma Formation of Xiphophorus

Melanoma formation in Xiphophorus is initiated by overexpression of an oncogenic version of the EGFR-related receptor tyrosine kinase Xmrk (Xiphophorus melanoma receptor kinase). High steady-state levels of Xmrk oncogene mRNA are found in malignant melanoma; however, this overabundance of transcripts appears to be not sufficient for manifestation of the full oncogenic potential of Xmrk. In addition, several amino acid exchanges cause the oncogenic receptor to be highly active, resulting in a strong tyrosine phosphorylation even without growth factor stimulation. Besides the receptor itself a Xmrk-specific signal transduction seems to be a critical part of the transformation machinery. Expression experiments in transgenic fish indicate that the Xmrk-mediated intracellular signalling is contributing to the cell-type specificity in development of hereditary melanoma in Xiphophorus.