SIGNAL-TRANSDUCTION BY THE ONCOGENIC RECEPTOR TYROSINE KINASE XMRK INMELANOMA FORMATION OF XIPHOPHORUS

Melanoma formation in Yiphophorus 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 Xmr k oncogene mRNA are found in malignant melanoma; however this overabun dance 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 stimu lation. Besides the receptor itself a Xmrk-specific signal transductio n seems to be a critical part of the transformation machinery. Express ion experiments in transgenic fish indicate that the Xmrk-mediated int racellular signalling is contributing to the cell-type specificity in development of hereditary melanoma in Xiphophorus.