Abstract
Human cells contain a tyrosine-specific protein kinase, pp60c-src, that is highly homologous to the oncogene product, pp60v-src, from Rous sarcoma virus but is of unknown function. The expression of human pp60c-src was examined in tissues obtained from human adults and fetuses of 20-32 weeks' gestational age. pp60c-src was quantitated in tissue extracts by measurement of its protein kinase activity by the use of the immune complex protein kinase assay. Brain showed the highest levels of pp60c-src protein kinase activity, but all other human tissues examined had significant levels. Fetal tissues, including brain, showed three- to eight-fold higher levels of pp60c-src kinase activity than the corresponding adult tissues. pp60c-src kinase was found to be uniformly distributed in the adult brain; frontal, occipital, and parietal cortex, and cerebellum expressed equivalent amounts of pp60c-src kinase activity. The protein kinase activity in human tissues exhibited properties characteristic of pp60c-src in other species, namely, tyrosine-specific phosphorylation of specific antibody heavy chains, autophosphorylation of a 60,000 Mr protein following immunoprecipitation with a monoclonal antibody specific for pp60src, and sensitivity to inhibition by P1,P4-di(adenosine-5')tetraphosphate. The high levels of human pp60c-src in fetal tissues, particularly in brain, suggest a possible function in developmental processes.
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- Blair D. G., Oskarsson M., Wood T. G., McClements W. L., Fischinger P. J., Vande Woude G. G. Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science. 1981 May 22;212(4497):941–943. doi: 10.1126/science.7233190. [DOI] [PubMed] [Google Scholar]
- Blithe D. L., Richert N. D., Pastan I. H. Purification of a tyrosine-specific protein kinase from Rous sarcoma virus-induced rat tumor. J Biol Chem. 1982 Jun 25;257(12):7135–7142. [PubMed] [Google Scholar]
- Brugge J. S., Erikson R. L. Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature. 1977 Sep 22;269(5626):346–348. doi: 10.1038/269346a0. [DOI] [PubMed] [Google Scholar]
- Chang E. H., Furth M. E., Scolnick E. M., Lowy D. R. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Nature. 1982 Jun 10;297(5866):479–483. doi: 10.1038/297479a0. [DOI] [PubMed] [Google Scholar]
- Chinkers M., Cohen S. Purified EGF receptor-kinase interacts specifically with antibodies to Rous sarcoma virus transforming protein. Nature. 1981 Apr 9;290(5806):516–519. doi: 10.1038/290516a0. [DOI] [PubMed] [Google Scholar]
- Collett M. S., Erikson R. L. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021–2024. doi: 10.1073/pnas.75.4.2021. [DOI] [PMC free article] [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]
- DeFeo D., Gonda M. A., Young H. A., Chang E. H., Lowy D. R., Scolnick E. M., Ellis R. W. Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328–3332. doi: 10.1073/pnas.78.6.3328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ek B., Westermark B., Wasteson A., Heldin C. H. Stimulation of tyrosine-specific phosphorylation by platelet-derived growth factor. Nature. 1982 Feb 4;295(5848):419–420. doi: 10.1038/295419a0. [DOI] [PubMed] [Google Scholar]
- Feldman R. A., Wang L. H., Hanafusa H., Balduzzi P. C. Avian sarcoma virus UR2 encodes a transforming protein which is associated with a unique protein kinase activity. J Virol. 1982 Apr;42(1):228–236. doi: 10.1128/jvi.42.1.228-236.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [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]
- Kasuga M., Karlsson F. A., Kahn C. R. Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science. 1982 Jan 8;215(4529):185–187. doi: 10.1126/science.7031900. [DOI] [PubMed] [Google Scholar]
- Kasuga M., Zick Y., Blithe D. L., Crettaz M., Kahn C. R. Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system. Nature. 1982 Aug 12;298(5875):667–669. doi: 10.1038/298667a0. [DOI] [PubMed] [Google Scholar]
- Kudlow J. E., Buss J. E., Gill G. N. Anti-pp60src antibodies are substrates for EGF-stimulated protein kinase. Nature. 1981 Apr 9;290(5806):519–521. doi: 10.1038/290519a0. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Levinson A. D., Oppermann H., Varmus H. E., Bishop J. M. The purified product of the transforming gene of avian sarcoma virus phosphorylates tyrosine. J Biol Chem. 1980 Dec 25;255(24):11973–11980. [PubMed] [Google Scholar]
- Levy B. T., Sorge L. K., Drum C. C., Maness P. F. Differential inhibition of cellular and viral pp60src kinase by P1,P4-di(adenosine-5')tetraphosphate. Mol Cell Biol. 1983 Oct;3(10):1718–1723. doi: 10.1128/mcb.3.10.1718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maness P. F., Engeser H., Greenberg M. E., O'Farrell M., Gall W. E., Edelman G. M. Characterization of the protein kinase activity of avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5028–5032. doi: 10.1073/pnas.76.10.5028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maness P. F., Perry M. E., Levy B. T. P1,P4-Di(adenosine-5')tetraphosphate inhibits phosphorylation of immunoglobulin G by Rous sarcoma virus pp60src. J Biol Chem. 1983 Apr 10;258(7):4055–4058. [PubMed] [Google Scholar]
- Müller R., Slamon D. J., Tremblay J. M., Cline M. J., Verma I. M. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature. 1982 Oct 14;299(5884):640–644. doi: 10.1038/299640a0. [DOI] [PubMed] [Google Scholar]
- Müller R., Tremblay J. M., Adamson E. D., Verma I. M. Tissue and cell type-specific expression of two human c-onc genes. Nature. 1983 Aug 4;304(5925):454–456. doi: 10.1038/304454a0. [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]
- Oppermann H., Levinson A. D., Varmus H. E., Levintow L., Bishop J. M. Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src). Proc Natl Acad Sci U S A. 1979 Apr;76(4):1804–1808. doi: 10.1073/pnas.76.4.1804. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oskarsson M., McClements W. L., Blair D. G., Maizel J. V., Vande Woude G. F. Properties of a normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney sarcoma virus. Science. 1980 Mar 14;207(4436):1222–1224. doi: 10.1126/science.6243788. [DOI] [PubMed] [Google Scholar]
- Parker R. C., Varmus H. E., Bishop J. M. Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src. Cell. 1984 May;37(1):131–139. doi: 10.1016/0092-8674(84)90308-8. [DOI] [PubMed] [Google Scholar]
- Purchio A. F. Evidence the pp60src, the product of the Rous sarcoma virus src gene, undergoes autophosphorylation. J Virol. 1982 Jan;41(1):1–7. doi: 10.1128/jvi.41.1.1-7.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richert N. D., Blithe D. L., Pastan I. Properties of the src kinase purified from Rous sarcoma virus-induced rat tumors. J Biol Chem. 1982 Jun 25;257(12):7143–7150. [PubMed] [Google Scholar]
- Rohrschneider L. R., Eisenman R. N., Leitch C. R. Identification of a Rous sarcoma virus transformation-related protein in normal avian and mammalian cells. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4479–4483. doi: 10.1073/pnas.76.9.4479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schartl M., Barnekow A. The expression in eukaryotes of a tyrosine kinase which is reactive with pp60v-src antibodies. Differentiation. 1982;23(2):109–114. doi: 10.1111/j.1432-0436.1982.tb01273.x. [DOI] [PubMed] [Google Scholar]
- Sefton B. M., Patschinsky T., Berdot C., Hunter T., Elliott T. Phosphorylation and metabolism of the transforming protein of Rous sarcoma virus. J Virol. 1982 Mar;41(3):813–820. doi: 10.1128/jvi.41.3.813-820.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shealy D. J., Erikson R. L. Human cells contain two forms of pp60c-src. Nature. 1981 Oct 22;293(5834):666–669. doi: 10.1038/293666a0. [DOI] [PubMed] [Google Scholar]
- Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [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]
- Takeya T., Hanafusa H. DNA sequence of the viral and cellular src gene of chickens. II. Comparison of the src genes of two strains of avian sarcoma virus and of the cellular homolog. J Virol. 1982 Oct;44(1):12–18. doi: 10.1128/jvi.44.1.12-18.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ushiro H., Cohen S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J Biol Chem. 1980 Sep 25;255(18):8363–8365. [PubMed] [Google Scholar]
- Yoshida M., Kawai S., Toyoshima K. Unifected avian cells contain structurally unrelated progenitors of viral sarcoma genes. Nature. 1980 Oct 16;287(5783):653–654. doi: 10.1038/287653a0. [DOI] [PubMed] [Google Scholar]