Abstract
Arachidonic acid (C20:4) metabolites were released constitutively from wild-type Rous sarcoma virus-transformed chicken embryo fibroblasts (CEF). 3H-labeled C20:4 and its metabolites were released from unstimulated and uninfected CEF only in response to stimuli such as serum, phorbol ester, or the calcium ionophore A23187. High-pressure liquid chromatography analysis showed that the radioactivity released from [3H]arachidonate-labeled transformed cells was contained in free arachidonate and in the cyclooxygenase products prostaglandin E2 and prostaglandin F2 alpha; no lipoxygenase products were identified. The release of C20:4 and its metabolites from CEF infected with pp60src deletion mutants was correlated with serum-independent DNA synthesis and with the expression of the mRNA for 9E3, a gene expressed in Rous sarcoma virus-transformed cells which has homology with several mitogenic and inflammatory peptides. 3H-labeled C20:4 release was not correlated with p36 phosphorylation, which argues against a role for this protein as a phospholipase A2 inhibitor. CEF infected with other oncogenic viruses encoding a tyrosine kinase also released C20:4, as did CEF infected with viruses that contained mos and ras; however, infection with a crk-containing virus did not result in stimulation of 3H-labeled C20:4 release, suggesting that utilization of this signaling pathway is specific for particular transformation stimuli.
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- Aderem A. A., Scott W. A., Cohn Z. A. A selective defect in arachidonic acid release from macrophage membranes in high potassium media. J Cell Biol. 1984 Oct;99(4 Pt 1):1235–1241. doi: 10.1083/jcb.99.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alonso T., Morgan R. O., Marvizon J. C., Zarbl H., Santos E. Malignant transformation by ras and other oncogenes produces common alterations in inositol phospholipid signaling pathways. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4271–4275. doi: 10.1073/pnas.85.12.4271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Antler A. M., Greenberg M. E., Edelman G. M., Hanafusa H. Increased phosphorylation of tyrosine in vinculin does not occur upon transformation by some avian sarcoma viruses. Mol Cell Biol. 1985 Jan;5(1):263–267. doi: 10.1128/mcb.5.1.263. [DOI] [PMC free article] [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]
- Benjamin C. W., Tarpley W. G., Gorman R. R. Loss of platelet-derived growth factor-stimulated phospholipase activity in NIH-3T3 cells expressing the EJ-ras oncogene. Proc Natl Acad Sci U S A. 1987 Jan;84(2):546–550. doi: 10.1073/pnas.84.2.546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benjamin C. W., Tarpley W. G., Gorman R. R. The lack of PDGE-stimulated PGE2 release from ras-transformed NIH-3T3 cells results from reduced phospholipase C but not phospholipase A2 activity. Biochem Biophys Res Commun. 1987 Jun 30;145(3):1254–1259. doi: 10.1016/0006-291x(87)91572-5. [DOI] [PubMed] [Google Scholar]
- Brugge J. S. The p35/p36 substrates of protein-tyrosine kinases as inhibitors of phospholipase A2. Cell. 1986 Jul 18;46(2):149–150. doi: 10.1016/0092-8674(86)90729-4. [DOI] [PubMed] [Google Scholar]
- Brunda M. J., Herberman R. B., Holden H. T. Inhibition of murine natural killer cell activity by prostaglandins. J Immunol. 1980 Jun;124(6):2682–2687. [PubMed] [Google Scholar]
- Burch R. M., Ma A. L., Axelrod J. Phorbol esters and diacylglycerols amplify bradykinin-stimulated prostaglandin synthesis in Swiss 3T3 fibroblasts. Possible independence from protein kinase C. J Biol Chem. 1988 Apr 5;263(10):4764–4767. [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]
- Cross F. R., Garber E. A., Hanafusa H. N-terminal deletions in Rous sarcoma virus p60src: effects on tyrosine kinase and biological activities and on recombination in tissue culture with the cellular src gene. Mol Cell Biol. 1985 Oct;5(10):2789–2795. doi: 10.1128/mcb.5.10.2789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross F. R., Garber E. A., Pellman D., Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol. 1984 Sep;4(9):1834–1842. doi: 10.1128/mcb.4.9.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross F. R., Hanafusa H. Local mutagenesis of Rous sarcoma virus: the major sites of tyrosine and serine phosphorylation of pp60src are dispensable for transformation. Cell. 1983 Sep;34(2):597–607. doi: 10.1016/0092-8674(83)90392-6. [DOI] [PubMed] [Google Scholar]
- Davidson F. F., Dennis E. A., Powell M., Glenney J. R., Jr Inhibition of phospholipase A2 by "lipocortins" and calpactins. An effect of binding to substrate phospholipids. J Biol Chem. 1987 Feb 5;262(4):1698–1705. [PubMed] [Google Scholar]
- Erikson E., Erikson R. L. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. Cell. 1980 Oct;21(3):829–836. doi: 10.1016/0092-8674(80)90446-8. [DOI] [PubMed] [Google Scholar]
- Fagan J. B., Sobel M. E., Yamada K. M., de Crombrugghe B., Pastan I. Effects of transformation on fibronectin gene expression using cloned fibronectin cDNA. J Biol Chem. 1981 Jan 10;256(1):520–525. [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Feldman R. A., Hanafusa T., Hanafusa H. Characterization of protein kinase activity associated with the transforming gene product of Fujinami sarcoma virus. Cell. 1980 Dec;22(3):757–765. doi: 10.1016/0092-8674(80)90552-8. [DOI] [PubMed] [Google Scholar]
- Feldman R. A., Wang E., Hanafusa H. Cytoplasmic localization of the transforming protein of Fujinami sarcoma virus: salt-sensitive association with subcellular components. J Virol. 1983 Feb;45(2):782–791. doi: 10.1128/jvi.45.2.782-791.1983. [DOI] [PMC free article] [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]
- Ginsburg D., Handin R. I., Bonthron D. T., Donlon T. A., Bruns G. A., Latt S. A., Orkin S. H. Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science. 1985 Jun 21;228(4706):1401–1406. doi: 10.1126/science.3874428. [DOI] [PubMed] [Google Scholar]
- Hammarström S. Prostaglandin production by normal and transformed 3T3 fibroblasts in cell culture. Eur J Biochem. 1977 Mar 15;74(1):7–12. doi: 10.1111/j.1432-1033.1977.tb11360.x. [DOI] [PubMed] [Google Scholar]
- Hanafusa H. Rapid transformation of cells by Rous sarcoma virus. Proc Natl Acad Sci U S A. 1969 Jun;63(2):318–325. doi: 10.1073/pnas.63.2.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirata F., Matsuda K., Notsu Y., Hattori T., del Carmine R. Phosphorylation at a tyrosine residue of lipomodulin in mitogen-stimulated murine thymocytes. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4717–4721. doi: 10.1073/pnas.81.15.4717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang K. S., Wallner B. P., Mattaliano R. J., Tizard R., Burne C., Frey A., Hession C., McGray P., Sinclair L. K., Chow E. P. Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase. Cell. 1986 Jul 18;46(2):191–199. doi: 10.1016/0092-8674(86)90736-1. [DOI] [PubMed] [Google Scholar]
- Hughes S. H., Greenhouse J. J., Petropoulos C. J., Sutrave P. Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol. 1987 Oct;61(10):3004–3012. doi: 10.1128/jvi.61.10.3004-3012.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jove R., Garber E. A., Iba H., Hanafusa H. Biochemical properties of p60v-src mutants that induce different cell transformation parameters. J Virol. 1986 Dec;60(3):849–857. doi: 10.1128/jvi.60.3.849-857.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamps M. P., Buss J. E., Sefton B. M. Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide substrates without inducing transformation. Cell. 1986 Apr 11;45(1):105–112. doi: 10.1016/0092-8674(86)90542-8. [DOI] [PubMed] [Google Scholar]
- Kawai S., Yoshida M., Segawa K., Sugiyama H., Ishizaki R., Toyoshima K. Characterization of Y73, an avian sarcoma virus: a unique transforming gene and its product, a phosphopolyprotein with protein kinase activity. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6199–6203. doi: 10.1073/pnas.77.10.6199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunkel S. L., Spengler M., May M. A., Spengler R., Larrick J., Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed] [Google Scholar]
- Levy J. B., Iba H., Hanafusa H. Activation of the transforming potential of p60c-src by a single amino acid change. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4228–4232. doi: 10.1073/pnas.83.12.4228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer B. J., Hamaguchi M., Hanafusa H. A novel viral oncogene with structural similarity to phospholipase C. Nature. 1988 Mar 17;332(6161):272–275. doi: 10.1038/332272a0. [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]
- Ritzi E. M., Stylos W. A. Prostaglandin production in cultures of BALB/3T3 and SV3T3 mouse fibroblasts. J Natl Cancer Inst. 1976 Mar;56(3):529–533. doi: 10.1093/jnci/56.3.529. [DOI] [PubMed] [Google Scholar]
- Rowe D. W., Moen R. C., Davidson J. M., Byers P. H., Bornstein P., Palmiter R. D. Correlation of procollagen mRNA levels in normal and transformed chick embryo fibroblasts with different rates of procollagen synthesis. Biochemistry. 1978 May 2;17(9):1581–1590. doi: 10.1021/bi00602a001. [DOI] [PubMed] [Google Scholar]
- Saga S., Chen W. T., Yamada K. M. Enhanced fibronectin receptor expression in Rous sarcoma virus-induced tumors. Cancer Res. 1988 Oct 1;48(19):5510–5513. [PubMed] [Google Scholar]
- Samuelsson B., Goldyne M., Granström E., Hamberg M., Hammarström S., Malmsten C. Prostaglandins and thromboxanes. Annu Rev Biochem. 1978;47:997–1029. doi: 10.1146/annurev.bi.47.070178.005025. [DOI] [PubMed] [Google Scholar]
- Saris C. J., Tack B. F., Kristensen T., Glenney J. R., Jr, Hunter T. The cDNA sequence for the protein-tyrosine kinase substrate p36 (calpactin I heavy chain) reveals a multidomain protein with internal repeats. Cell. 1986 Jul 18;46(2):201–212. doi: 10.1016/0092-8674(86)90737-3. [DOI] [PubMed] [Google Scholar]
- Seemann D., Fürstenberger G., Marks F. Effects of the skin mitogens tumor-promotor 12-O-tetradecanoylphorbol 13-acetate and divalent-cation-ionophore A23187 on ion fluxes and membrane potential in a murine epidermal cell line (HEL30) and in 3T3 fibroblasts. Eur J Biochem. 1983 Dec 15;137(3):485–494. doi: 10.1111/j.1432-1033.1983.tb07852.x. [DOI] [PubMed] [Google Scholar]
- Stahl M. L., Ferenz C. R., Kelleher K. L., Kriz R. W., Knopf J. L. Sequence similarity of phospholipase C with the non-catalytic region of src. Nature. 1988 Mar 17;332(6161):269–272. doi: 10.1038/332269a0. [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]
- Suh P. G., Ryu S. H., Moon K. H., Suh H. W., Rhee S. G. Cloning and sequence of multiple forms of phospholipase C. Cell. 1988 Jul 15;54(2):161–169. doi: 10.1016/0092-8674(88)90548-x. [DOI] [PubMed] [Google Scholar]
- Taffet S. M., Russell S. W. Macrophage-mediated tumor cell killing: regulation of expression of cytolytic activity by prostaglandin E. J Immunol. 1981 Feb;126(2):424–427. [PubMed] [Google Scholar]
- Tamkun J. W., DeSimone D. W., Fonda D., Patel R. S., Buck C., Horwitz A. F., Hynes R. O. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 1986 Jul 18;46(2):271–282. doi: 10.1016/0092-8674(86)90744-0. [DOI] [PubMed] [Google Scholar]
- Vicentini L. M., Villereal M. L. Serum, bradykinin and vasopressin stimulate release of inositol phosphates from human fibroblasts. Biochem Biophys Res Commun. 1984 Sep 17;123(2):663–670. doi: 10.1016/0006-291x(84)90280-8. [DOI] [PubMed] [Google Scholar]
- Walker C., Kristensen F., Bettens F., deWeck A. L. Lymphokine regulation of activated (G1) lymphocytes. I. Prostaglandin E2-induced inhibition of interleukin 2 production. J Immunol. 1983 Apr;130(4):1770–1773. [PubMed] [Google Scholar]
- Young M. R., Henderson S. Enhancement in immunity of tumor bearing mice by immunization against prostaglandin E2. Immunol Commun. 1982;11(5):345–356. doi: 10.3109/08820138209050734. [DOI] [PubMed] [Google Scholar]
- Zehner Z. E., Paterson B. M. Vimentin gene expression during myogenesis: two functional transcripts from a single copy gene. Nucleic Acids Res. 1983 Dec 10;11(23):8317–8332. doi: 10.1093/nar/11.23.8317. [DOI] [PMC free article] [PubMed] [Google Scholar]