Abstract
The SRC gene is the prototype for a family of closely related genes whose products have protein-tyrosine kinase activity. We recently described another member of this family, designated FYN, whose cDNA was isolated from normal human fibroblasts. To examine the possible role of FYN as an oncogene, we investigated the effects of FYN overexpression on NIH 3T3 cells. Our findings demonstrate that normal FYN overexpression induces morphologic transformation and anchorage-independent growth. In addition, at relatively low frequency, FYN acquired properties of a dominant-acting oncogene capable of inducing the fully tumorigenic phenotype. Genetic changes associated with the conversion of normal FYN cDNA into a transforming gene with high focus-forming activity were localized to the carboxyl-terminal region of its translational product.
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Selected References
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- Barnekow A., Gessler M. Activation of the pp60c-src kinase during differentiation of monomyelocytic cells in vitro. EMBO J. 1986 Apr;5(4):701–705. doi: 10.1002/j.1460-2075.1986.tb04270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
- Cartwright C. A., Eckhart W., Simon S., Kaplan P. L. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell. 1987 Apr 10;49(1):83–91. doi: 10.1016/0092-8674(87)90758-6. [DOI] [PubMed] [Google Scholar]
- Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
- Cooper J. A., Gould K. L., Cartwright C. A., Hunter T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986 Mar 21;231(4744):1431–1434. doi: 10.1126/science.2420005. [DOI] [PubMed] [Google Scholar]
- Cotton P. C., Brugge J. S. Neural tissues express high levels of the cellular src gene product pp60c-src. Mol Cell Biol. 1983 Jun;3(6):1157–1162. doi: 10.1128/mcb.3.6.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Courtneidge S. A. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation. EMBO J. 1985 Jun;4(6):1471–1477. doi: 10.1002/j.1460-2075.1985.tb03805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fults D. W., Towle A. C., Lauder J. M., Maness P. F. pp60c-src in the developing cerebellum. Mol Cell Biol. 1985 Jan;5(1):27–32. doi: 10.1128/mcb.5.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Golden A., Nemeth S. P., Brugge J. S. Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity. Proc Natl Acad Sci U S A. 1986 Feb;83(4):852–856. doi: 10.1073/pnas.83.4.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter T., Cooper J. A. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. doi: 10.1146/annurev.bi.54.070185.004341. [DOI] [PubMed] [Google Scholar]
- Inoue K., Ikawa S., Semba K., Sukegawa J., Yamamoto T., Toyoshima K. Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9. Oncogene. 1987;1(3):301–304. [PubMed] [Google Scholar]
- Jacobs C., Rübsamen H. Expression of pp60c-src protein kinase in adult and fetal human tissue: high activities in some sarcomas and mammary carcinomas. Cancer Res. 1983 Apr;43(4):1696–1702. [PubMed] [Google Scholar]
- Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katamine S., Notario V., Rao C. D., Miki T., Cheah M. S., Tronick S. R., Robbins K. C. Primary structure of the human fgr proto-oncogene product p55c-fgr. Mol Cell Biol. 1988 Jan;8(1):259–266. doi: 10.1128/mcb.8.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawakami T., Pennington C. Y., Robbins K. C. Isolation and oncogenic potential of a novel human src-like gene. Mol Cell Biol. 1986 Dec;6(12):4195–4201. doi: 10.1128/mcb.6.12.4195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kitamura N., Kitamura A., Toyoshima K., Hirayama Y., Yoshida M. Avian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus. Nature. 1982 May 20;297(5863):205–208. doi: 10.1038/297205a0. [DOI] [PubMed] [Google Scholar]
- Kmiecik T. E., Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell. 1987 Apr 10;49(1):65–73. doi: 10.1016/0092-8674(87)90756-2. [DOI] [PubMed] [Google Scholar]
- Levy B. T., Sorge L. K., Meymandi A., Maness P. F. pp60c-src Kinase is in chick and human embryonic tissues. Dev Biol. 1984 Jul;104(1):9–17. doi: 10.1016/0012-1606(84)90031-9. [DOI] [PubMed] [Google Scholar]
- Marth J. D., Peet R., Krebs E. G., Perlmutter R. M. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. doi: 10.1016/0092-8674(85)90169-2. [DOI] [PubMed] [Google Scholar]
- Naharro G., Robbins K. C., Reddy E. P. Gene product of v-fgr onc: hybrid protein containing a portion of actin and a tyrosine-specific protein kinase. Science. 1984 Jan 6;223(4631):63–66. doi: 10.1126/science.6318314. [DOI] [PubMed] [Google Scholar]
- Pavlakis G. N., Hamer D. H. Regulation of a metallothionein-growth hormone hybrid gene in bovine papilloma virus. Proc Natl Acad Sci U S A. 1983 Jan;80(2):397–401. doi: 10.1073/pnas.80.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piwnica-Worms H., Saunders K. B., Roberts T. M., Smith A. E., Cheng S. H. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. doi: 10.1016/0092-8674(87)90757-4. [DOI] [PubMed] [Google Scholar]
- Quintrell N., Lebo R., Varmus H., Bishop J. M., Pettenati M. J., Le Beau M. M., Diaz M. O., Rowley J. D. Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells. Mol Cell Biol. 1987 Jun;7(6):2267–2275. doi: 10.1128/mcb.7.6.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Semba K., Nishizawa M., Miyajima N., Yoshida M. C., Sukegawa J., Yamanashi Y., Sasaki M., Yamamoto T., Toyoshima K. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5459–5463. doi: 10.1073/pnas.83.15.5459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
- Sorge L. K., Levy B. T., Maness P. F. pp60c-src is developmentally regulated in the neural retina. Cell. 1984 Feb;36(2):249–257. doi: 10.1016/0092-8674(84)90218-6. [DOI] [PubMed] [Google Scholar]
- Sukegawa J., Semba K., Yamanashi Y., Nishizawa M., Miyajima N., Yamamoto T., Toyoshima K. Characterization of cDNA clones for the human c-yes gene. Mol Cell Biol. 1987 Jan;7(1):41–47. doi: 10.1128/mcb.7.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeya T., Hanafusa H. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell. 1983 Mar;32(3):881–890. doi: 10.1016/0092-8674(83)90073-9. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Voronova A. F., Sefton B. M. Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion. Nature. 1986 Feb 20;319(6055):682–685. doi: 10.1038/319682a0. [DOI] [PubMed] [Google Scholar]
- Wigler M., Silverstein S., Lee L. S., Pellicer A., Cheng Y. c., Axel R. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell. 1977 May;11(1):223–232. doi: 10.1016/0092-8674(77)90333-6. [DOI] [PubMed] [Google Scholar]
- Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N., Matsubara K., Yamamoto T., Toyoshima K. The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck. Mol Cell Biol. 1987 Jan;7(1):237–243. doi: 10.1128/mcb.7.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziegler S. F., Marth J. D., Lewis D. B., Perlmutter R. M. Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin. Mol Cell Biol. 1987 Jun;7(6):2276–2285. doi: 10.1128/mcb.7.6.2276. [DOI] [PMC free article] [PubMed] [Google Scholar]