Abstract
Induction of the transformation-related gene 9E3 by the v-src and v-fps gene products (v-Src and v-Fps) is blocked in chicken embryo fibroblasts depleted of protein kinase C (PKC). PKC agonists induce 9E3 gene expression. Protein kinase inhibitors block v-Src- and v-Fps-induced 9E3 gene expression with the same dose-response curves seen for PKC agonist-induced 9E3 gene expression. These data suggest that v-Src and v-Fps use a PKC-mediated signal-transduction pathway to induce expression of the transformation-related 9E3 gene. Consistent with this hypothesis, we find that both v-Src and v-Fps rapidly induce phosphorylation of a 67-kDa PKC substrate.
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Selected References
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- Aderem A. A., Albert K. A., Keum M. M., Wang J. K., Greengard P., Cohn Z. A. Stimulus-dependent myristoylation of a major substrate for protein kinase C. Nature. 1988 Mar 24;332(6162):362–364. doi: 10.1038/332362a0. [DOI] [PubMed] [Google Scholar]
- Albert K. A., Nairn A. C., Greengard P. The 87-kDa protein, a major specific substrate for protein kinase C: purification from bovine brain and characterization. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7046–7050. doi: 10.1073/pnas.84.20.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ashendel C. L. The phorbol ester receptor: a phospholipid-regulated protein kinase. Biochim Biophys Acta. 1985 Sep 9;822(2):219–242. doi: 10.1016/0304-4157(85)90009-7. [DOI] [PubMed] [Google Scholar]
- Bedard P. A., Alcorta D., Simmons D. L., Luk K. C., Erikson R. L. Constitutive expression of a gene encoding a polypeptide homologous to biologically active human platelet protein in Rous sarcoma virus-transformed fibroblasts. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6715–6719. doi: 10.1073/pnas.84.19.6715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiarugi V., Porciatti F., Pasquali F., Magnelli L., Giannelli S., Ruggiero M. Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts. Oncogene. 1987;2(1):37–40. [PubMed] [Google Scholar]
- Davis R. J., Czech M. P. Stimulation of epidermal growth factor receptor threonine 654 phosphorylation by platelet-derived growth factor in protein kinase C-deficient human fibroblasts. J Biol Chem. 1987 May 15;262(14):6832–6841. [PubMed] [Google Scholar]
- Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
- Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
- Foster D. A., Shibuya M., Hanafusa H. Activation of the transformation potential of the cellular fps gene. Cell. 1985 Aug;42(1):105–115. doi: 10.1016/s0092-8674(85)80106-9. [DOI] [PubMed] [Google Scholar]
- Gould K. L., Woodgett J. R., Cooper J. A., Buss J. E., Shalloway D., Hunter T. Protein kinase C phosphorylates pp60src at a novel site. Cell. 1985 Oct;42(3):849–857. doi: 10.1016/0092-8674(85)90281-8. [DOI] [PubMed] [Google Scholar]
- Hanafusa T., Mathey-Prevot B., Feldman R. A., Hanafusa H. Mutants of Fujinami sarcoma virus which are temperature sensitive for cellular transformation and protein kinase activity. J Virol. 1981 Apr;38(1):347–355. doi: 10.1128/jvi.38.1.347-355.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hatch C. L., Bonner W. M. Direct analysis of RNA in whole cell and cytoplasmic extracts by gel electrophoresis. Anal Biochem. 1987 Apr;162(1):283–290. doi: 10.1016/0003-2697(87)90038-8. [DOI] [PubMed] [Google Scholar]
- Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [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]
- Ishikawa T., Inagaki M., Watanabe M., Hidaka H. Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase. J Pharmacol Exp Ther. 1985 Nov;235(2):495–499. [PubMed] [Google Scholar]
- Kataoka T., Powers S., Cameron S., Fasano O., Goldfarb M., Broach J., Wigler M. Functional homology of mammalian and yeast RAS genes. Cell. 1985 Jan;40(1):19–26. doi: 10.1016/0092-8674(85)90304-6. [DOI] [PubMed] [Google Scholar]
- Kawamoto S., Hidaka H. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem Biophys Res Commun. 1984 Nov 30;125(1):258–264. doi: 10.1016/s0006-291x(84)80362-9. [DOI] [PubMed] [Google Scholar]
- Lim R. W., Varnum B. C., Herschman H. R. Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. Oncogene. 1987;1(3):263–270. [PubMed] [Google Scholar]
- Loomis C. R., Bell R. M. Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C. J Biol Chem. 1988 Feb 5;263(4):1682–1692. [PubMed] [Google Scholar]
- Martins T. J., Sugimoto Y., Erikson R. L. Dissociation of inositol trisphosphate from diacylglycerol production in Rous sarcoma virus-transformed fibroblasts. J Cell Biol. 1989 Feb;108(2):683–691. doi: 10.1083/jcb.108.2.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer B. J., Jove R., Krane J. F., Poirier F., Calothy G., Hanafusa H. Genetic lesions involved in temperature sensitivity of the src gene products of four Rous sarcoma virus mutants. J Virol. 1986 Dec;60(3):858–867. doi: 10.1128/jvi.60.3.858-867.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCaffrey P., Ran W., Campisi J., Rosner M. R. Two independent growth factor-generated signals regulate c-fos and c-myc mRNA levels in Swiss 3T3 cells. J Biol Chem. 1987 Feb 5;262(4):1442–1445. [PubMed] [Google Scholar]
- Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
- Pellman D., Garber E. A., Cross F. R., Hanafusa H. Fine structural mapping of a critical NH2-terminal region of p60src. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1623–1627. doi: 10.1073/pnas.82.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pike L. J., Eakes A. T. Epidermal growth factor stimulates the production of phosphatidylinositol monophosphate and the breakdown of polyphosphoinositides in A431 cells. J Biol Chem. 1987 Feb 5;262(4):1644–1651. [PubMed] [Google Scholar]
- Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
- Rozengurt E. Early signals in the mitogenic response. Science. 1986 Oct 10;234(4773):161–166. doi: 10.1126/science.3018928. [DOI] [PubMed] [Google Scholar]
- Sagara J., Yamada K. M., Kakunaga T. Induction of an unusual type of shared phosphorylation in human and avian cells by tumor-promoting phorbol esters or transformation. Cancer Res. 1986 Oct;46(10):5291–5296. [PubMed] [Google Scholar]
- Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
- Sasakawa N., Ishii K., Yamamoto S., Kato R. Differential effects of protein kinase C activators on carbamylcholine- and high K+-induced rises in intracellular free calcium concentration in cultured adrenal chromaffin cells. Biochem Biophys Res Commun. 1986 Sep 30;139(3):903–909. doi: 10.1016/s0006-291x(86)80263-7. [DOI] [PubMed] [Google Scholar]
- Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
- Sugano S., Stoeckle M. Y., Hanafusa H. Transformation by Rous sarcoma virus induces a novel gene with homology to a mitogenic platelet protein. Cell. 1987 May 8;49(3):321–328. doi: 10.1016/0092-8674(87)90284-4. [DOI] [PubMed] [Google Scholar]
- Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
- Wolfman A., Wingrove T. G., Blackshear P. J., Macara I. G. Down-regulation of protein kinase C and of an endogenous 80-kDa substrate in transformed fibroblasts. J Biol Chem. 1987 Dec 5;262(34):16546–16552. [PubMed] [Google Scholar]