Subcellular fate of the lnt-2 oncoprotein is determined by choice of initiation codon

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Abstract
FIBROBLAST growth factors (FGFs) have been implicated in many aspects of cell growth and differentiation both in normal and neoplastic settings1,2. For example, the mouse int-2 gene, which encodes an FGF-related product3, is a frequent target of proviral activation in carcinomas induced by mouse mammary tumour virus4,5, but apparently functions at discrete stages of normal embryonic development6,7. Six classes of int-2 messenger RNA have been identified in embryonic cells, each of which is predicted to encode the same 245-amino-acid protein8–10. But all known int-2 transcripts include sequences upstream of the AUG codon presumed to be the initiation codon. Here we report an additional N-terminally extended int-2 gene product initiated at an in-frame CUG codon. In COS-1 cells transiently transfected with appropriate int-2 complementary DNAs, the AUG-initiated product is found predominantly in the secretory pathway, whereas the CUG-initiated form is localized to the nucleus. These data indicate that the Int-2 oncoprotein could influence cellular behaviour by two distinct mechanisms.