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Differential expression and translocation of protein tyrosine phosphatase 1B-related proteins in ME-180 tumor cells expressing apoptotic sensitivity and resistance to tumor necrosis factor: potential interaction with epidermal growth factor receptor

Abstract

Tumor necrosis factor (TNF)-induced apoptosis can be inhibited by overexpression of specific tyrosine kinases or activation of tyrosine kinase cascades, suggesting potential antagonism between apoptotic and tyrosine kinase signaling processes. In this report, the effects of TNF on EGF receptor tyrosine phosphorylation in ME-180 cell variants selected for apoptotic sensitivity (Sen) or resistance (Res) to TNF, previously shown to differentially express EGFr, were examined. Prior to the onset of apoptosis, TNF caused a significant reduction in the level of EGFr tyrosine phosphorylation in Sen cells but mediated only limited suppression of EGFr tyrosine phosphorylation in apoptotically resistant Res cells. In vitro incubation of cellular membranes with TNF derived from Sen cells stimulated a resident protein tyrosine phosphatase (PTP) activity which was able to dephosphorylate EGFr or tyrosine phosphopeptides mimicking an EGFr autophosphorylation site. In membrane preparations, PTP1B complexed with tyrosine phosphorylated EGFr and this association was disrupted by TNF through an apparent stimulation of PTP activity and turnover of phosphotyrosine. Intrinsic enzymatic activity of PTP1B was 2 – 3-fold higher in Sen versus Res cell lysates and a family of PTP1B-related proteins with altered C-termini was found to be highly expressed in Sen cells but absent or expressed at reduced levels in Res cells. Cytoplasmic extracts of Sen cells contained PTP1B-like proteins and TNF incubation resulted in the time dependent accumulation of PTP1B-like proteins in Sen cells but did not effect these proteins in Res cells. Together, these results suggest that specific changes in expression and subcellular distribution of phosphotyrosine modulatory proteins may play a role in conveying intrinsic apoptotic sensitivity to TNF in some tumor cell types.

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Abbreviations

EGF:

epidermal growth factor

TNF:

tumor necrosis factor

PTP:

protein tyrosine phosphatase

References

  • Aggarwal BB, Totpal K, Ali-Osman F, Budde RJ and Pocsik E. . 1994 FEBS Lett. 345: 219–224.

  • Atherton E and Sheppard RC. . 1989 Solid Phase Peptide Synthesis, A Practical Approach IRL Press, Oxford.

    Google Scholar 

  • Bandyopadhyay D, Kusari A, Kenner KA, Liu F, Chernoff J, Gustafson TA and Kusari J. . 1997 J. Biol. Chem. 272: 1639–1645.

  • Boldin MP, Goncharov TM, Goltsev YV and Wallach D. . 1996 Cell 85: 803–815.

  • Byon JCH, Kenner KA, Kusari AB and Kusari J. . 1997 Proc. Soc. Exp. Biol. Med. 216: 1–20.

  • Carson DA and Ribeiro JM. . 1993 Lancet 341: 1251–1254.

  • Chang DJ, Ringold GM and Heller RA. . 1992 Biochem. Biophys. Res. Commun. 188: 538–546.

  • Chen YR, Meyer CF and Tan TH. . 1996a J. Biol. Chem. 271: 631–634.

  • Chen YR, Wang X, Templeton D, Davis RJ and Tan T-H. . 1996b J. Biol. Chem. 271: 31929–31936.

  • Cleveland JL and Ihle JN. . 1995 Cell 81: 479–482.

  • Cooper JA, Sefton BM and Hunter T. . 1983 Meths. Enzymol. 99: 387–402.

  • Donato NJ, Rosenblum MG and Steck PA. . 1992 Cell Growth & Differen. 3: 259–268.

  • Donato NJ, Yan DH, Hung MC and Rosenblum MG. . 1993 Cell Growth Differen. 4: 411–419.

  • Donato NJ and Perez M. . 1998 J. Biol. Chem. 273: 5067–5072.

  • Dowd D. . 1995 Adv. Second Mess. Phospho. Res. 30: 255–280.

  • Dubrez L, Savoy I, Hamman A and Solavy E. . 1996 EMBO J. 15: 5504–5512.

  • Eastman A. . 1995 Sem. Cancer Biol. 6: 45–52.

  • Eischen CM, Dick CJ and Leibson PJ. . 1994 J. Immunol. 153: 1947–1954.

  • Enari M, Talanian R, Wong W and Nagata S. . 1996 Nature 380: 723–726.

  • Flint AJ, Grebbink MFGB, Franza BR, Hill DE and Tonks NK. . 1993 EMBO J. 12: 1937–1946.

  • Flint AJ, Tiganis T, Barford D and Tonks NK. . 1997 Proc. Natl. Acad. Sci. USA 94: 1680–1685.

  • Frangioni JV, Beahm PH, Shifrin V, Jost CA and Neel BG. . 1992 Cell 68: 545–560.

  • Frangioni JV, Oda A, Smith M, Salzman EW and Neel BG. . 1993 EMBO J. 12: 4843–4856.

  • Fraser A and Evans G. . 1996 Cell 85: 781–784.

  • Freeman BA and Crapo JD. . 1982 Lab. Invest. 47: 412–426.

  • Gagliardini V, Fernandez PA, Lee RKK, Drexler HCA, Rotello RJ, Fishman MC and Yuan J. . 1994 Science 263: 826–828.

  • Garcia-Lloret MI, Yui J, Winkler-Lowen B and Guilbert LJ. . 1996 J. Cell. Physiol. 16: 324–332.

  • Gardner AM and Johnson GL. . 1996 J. Biol. Chem. 271: 14560–14566.

  • Goossens V, Grooten J, De Vos K and Fiers W. . 1995 Proc. Natl. Acad. Sci. USA 92: 8115–8119.

  • Henkart PA. . 1996 Immunity 4: 195–201.

  • Hudziak RM, Lewis GD, Shalaby MR, Eessalu TE, Aggarwal BB, Ullrich A and Shephard HM. . 1988 Proc. Natl. Acad. Sci. USA 85: 5102–5106.

  • Hsu H, Xiong J and Goeddel DV. . 1995 Cell 81: 495–504.

  • Jaattela M, Benedict M, Tewari M, Shayman JA and Dixit VM. . 1995 Oncogene 10: 2297–2305.

  • Kenner KA, Anyanwu E, Olefsky JM and Kusari J. . 1996 J. Biol. Chem. 271: 19810–19816.

  • Korsmeyer SJ. . 1995 Trends Genet. 11: 101–105.

  • Krippner A, Matsuno-Yagi A, Gottlieb RA and Babior BM. . 1996 J. Biol. Chem. 271: 21629–21636.

  • Lammers R, Bossenmaier B, Cool DE, Tonks NK, Schlessinger J, Fischer EH and Ullrich A. . 1993 J. Biol. Chem. 268: 22456–22462.

  • Liles WC, Kiener PA, Ledbetter JA, Aruffo A and Klebanoff SJ. . 1996 J. Exp. Med. 184: 429–440.

  • Liu F, Hill DA and Chernoff J. . 1996 J. Biol. Chem. 271: 31290–31295.

  • Liu F and Chernoff J. . 1997 Biochem. J. 327: 139–145.

  • Liu F, Sells MA and Chernoff J. . 1998 Mol. Cell. Biol. 18: 250–259.

  • Liu Z, Hsu H, Goeddel DV and Karin M. . 1996 Cell 87: 565–576.

  • Lumelsky NL and Schwartz BS. . 1996 Cancer Res. 56: 3909–3914.

  • Maegawa H, Ide R, Hasegawa M, Ugi S, Egawa K, Iwanishi M, Kikkawa R, Shigeta Y and Kashiwagi A. . 1995 J. Biol. Chem. 270: 7724–7730.

  • Merlo GR, Basolo F, Fiore L, Duboc L and Hynes NE. . 1995 J. Cell Biol. 128: 1185–1196.

  • Migita K, Eguchi K, Kawabe Y and Nagataki S. . 1995 Immunol. 85: 550–555.

  • Milarski KL, Zhu F, Pearl CG, McNamara DJ, Dobrusin EM, MacLean D, Thieme-Sefler A, Zhang ZY, Sawyer T, Decker SJ, Dixon JE and Saltiel AR. . 1993 J. Biol. Chem. 268: 23634–23639.

  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Schevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME and Dixit VM. . 1996 Cell 85: 817–827.

  • Nabel G and Baltimore D. . 1987 Nature 326: 711–713.

  • Nagata S and Golstein P. . 1995 Science 267: 1449–1456.

  • Nicotera P, Bellomo G and Orrenius S. . 1992 Ann. Rev. Pharmacol. Toxicol. 32: 449–470.

  • Nishikawa K, Rotbein J, Vijjeswarapu D, Owen-Schaub L, Rosenblum MG and Donato NJ. . 1994 Lymphokine and Cytokine Res. 13: 37–45.

  • Perez M and Donato NJ. . 1996 J. Interferon Cytokine Res. 16: 307–314.

  • Rock MT, Brooks WH and Roszman TL. . 1997 J. Biol. Chem. 272: 33377–33383.

  • Santana P, Pena LA, Haimovitz-Friedman A, Martin S, Green D, McLoughlin M, Gordon-Cardo C, Schuchman EH, Fuks Z and Kolesnick R. . 1996 Cell 86: 189–199.

  • Schieven GL, Wahl AF, Mydral S, Grosmaire L and Ledbetter JA. . 1995 J. Biol. Chem. 270: 20824–20831.

  • Schreck R, Rieber P and Baeuerle PA. . 1991 EMBO J. 10: 2247–2258.

  • Schreiber E, Mathias P, Muller MM and Schaffner W. . 1989 Nucleic Acids Res. 17: 6419.

  • Shephard HM and Lewis GD. . 1988 J. Clin. Immunol. 8: 333–341.

  • Shifrin VI, Davis RJ and Neel BG. . 1997 J. Biol. Chem. 272: 2957–2962.

  • Stefanis L, Park DS, Yan CYI, Farinelli SE, Troy CM, Shelanski MD and Green LA. . 1996 J. Biol. Chem. 271: 30663–30671.

  • Su X, Zhou T, Wang Z, Yang P, Jope RS and Mountz JD. . 1995 Immunity 2: 353–362.

  • Sugarman BJ, Lewis GD, Eessalu TE, Aggarwal BB and Shepard HM. . 1987 Cancer Res. 47: 781–786.

  • Tewari M and Dixit VM. . 1995 J. Biol. Chem. 270: 3255–3260.

  • Tilly JL, Bilig H, Kowalski KI and Hsueh A. . 1992 J. Mol. Endocrin. 6: 1942–1950.

  • Tonks NK, Diltz GD and Fischer EH. . 1988 J. Biol. Chem. 263: 6722–6730.

  • Tonks NK and Neel BG. . 1996 Cell 87: 365–368.

  • Warren S, Torti SV and Torti FM. . 1993 Lymphokine & Cytokine Res. 12: 75–80.

  • Wiener JR, Kerns B-JM, Harvey EL, Conaway MR, Igelhart JD, Berchunk A and Bast RC. . 1994 J. Natl. Cancer Inst. 86: 372–378.

  • Wong GHW, Elwell JH, Oberly LW and Goeddel DV. . 1989 Cell 58: 923–931.

  • Woodford-Thomas TA, Rhodes JD and Dixon JE. . 1992 J. Cell Biol. 117: 401–414.

  • Wu X, Fan Z, Masui H, Rosen N and Mendelsohn J. . 1995 J. Clin. Invest. 95: 1897–1905.

  • Wu Y, Tewari M, Cui S and Rubin R. . 1996 J. Cell. Physiol. 168: 499–509.

  • Yousefi S, Green DR, Blaser K and Simon HU. . 1994 Proc. Natl. Acad. Sci. USA 91: 10868–10872.

  • Zhai YF, Beittenmiller H, Wang B, Gould MN, Oakley C, Esselman WJ and Welsch CW. . 1993 Cancer Res. 53: 2272–2278.

  • Zimmerman RJ, Chan A and Leadon SA. . 1989 Cancer Res. 49: 1644–1648.

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Acknowledgements

This research was supported by grants from the National Institutes of Health (CA48906 and CA73018) and was conducted in part by The Clayton Foundation for Research. [TGBTG].

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Perez, M., Haschke, B. & Donato, N. Differential expression and translocation of protein tyrosine phosphatase 1B-related proteins in ME-180 tumor cells expressing apoptotic sensitivity and resistance to tumor necrosis factor: potential interaction with epidermal growth factor receptor. Oncogene 18, 967–978 (1999). https://doi.org/10.1038/sj.onc.1202368

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