Specific activation of a STAT family member in Xiphophorus melanoma cells

Melanoma formation in the teleost fish Xiphophorus is caused by the uncontr olled activity of the genetically defined tumor locus Tu. The critical comp onent of this locus is the Xmrh oncogene encoding a subclass I receptor tyr osine kinase. Overexpression and constitutive activation of the Xmrk recept or triggers a set of specific signal transduction events eventually resulti ng in the malignant phenotype. We have identified a melanoma-specific DNA-p rotein complex which seems to depend on Xmrk activation as shown in a heter ologous cell system. The critical component of this complex, which directs transcriptional activation in the melanoma cells, proved to be a fish homol ogue of STAT5. Two other STAT factors, STAT1 and STAT3, implied in signalin g by the Xmrk-related EGF receptor, were not activated in this particular c ell type. Thus, Xmrk initiates very specific signaling pathways and transcr iptional responses in Xiphophorus melanoma. (C) 1999 Academic Press.