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.
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References
Gospodarowicz, D., Ferrar, N., Schweigerer, L. & Neufeld, G. Endocrine Reviews 8, 95–114 (1987).
Rifkin, D. B. & Moscatelli, D. J. cell. Biol. 109, 1–6 (1989).
Dickson, C. & Peters, G. Nature 326, 833 (1987).
Dickson, C., Smith, R., Brookes, S. & Peters, G. Cell 37, 529–536 (1984).
Peters, G. & Dickson, C. in Cellular and Molecular Biology of Mammary Cancer eds D. Medina et al. 307–319 (Plenum, New York, 1987).
Wilkinson, D. G., Peters, G., Dickson, C. & McMahon, A. P. EMBO J. 7, 691–695 (1988).
Wilkinson, D. G., Bhatt, S. & McMahon, A. P. Development 105, 131–136 (1989).
Moore, R. et al. EMBO J. 5, 919–924 (1986).
Smith, R., Peters, G. & Dickson, C. EMBO J. 7, 1013–1022 (1988).
Mansour, S. L. & Martin, G. R. EMBO J. 7, 2035–2041 (1988).
Dixon, M. et al. Molec. cell. Biol. 9, 4896–4902 (1989).
Hann, S. R., King, M. W., Bentley, D. L., Anderson, C. W. & Eisenman, R. N. Cell 52, 185–195 (1988).
Peabody, D. S. J. biol. Chem. 264, 5031–5035 (1989).
Yoshida, T. et al. Proc. nant. Acad. Sci. U.S.A. 84, 7305–7309 (1987).
Delli-Bovi, P. et al. Molec. cell. Biol. 8, 2933–2941 (1988).
Zhan, X., Bates, B., Hu, X. & Goldfarb, M. Molec. cell. Biol. 8, 3487–3495 (1988).
Harlow, E., Crawford, L. V., Pim, D. C. & Williamson, N. M. J. Virol. 39, 861–869 (1981).
Hortsch, M. & Meyer, D. Eur. J. Biochem. 150, 559–564 (1985).
Dingwall, C. & Laskey, R. A. A. Rev. Cell Biol. 2, 367–390 (1986).
Brookes, S., Smith, R., Casey, G., Dickson, C. & Peters, G. Oncogene 4, 429–436 (1989).
Prats, H. et al. Proc. natn. Acad. Sci. U.S.A. 86, 1836–1840 (1989).
Florkiewicz, R. Z. & Sommer, A. Proc. natn. Acad. Sci. U.S.A. 86, 3978–3981 (1989).
Bouche, G. et al. Proc. natn. Acad. Sci. U.S.A. 84, 6770–6774 (1987).
Yeh, H.-J., Pierce, G. F. & Deuel, T. F. Proc. natn. Acad. Sci. U.S.A. 84, 2317–2321 (1987).
Lee, B. A., Maher, D. W., Hannink, M. & Donoghue, D. J. Molec. cell. Biol. 7, 3527–3537 (1987).
Spence, A. M. et al. Proc. natn. Acad. Sci. U.S.A. 86, 7843–7847 (1989).
Kozak, M. J. Cell Biol. 108, 229–241 (1989).
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Acland, P., Dixon, M., Peters, G. et al. Subcellular fate of the lnt-2 oncoprotein is determined by choice of initiation codon. Nature 343, 662–665 (1990). https://doi.org/10.1038/343662a0
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DOI: https://doi.org/10.1038/343662a0