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Multidrug Resistant Gene 1 Product in Human T Cell Subsets: Role of Protein Kinase C Isoforms and Regulation by Cyclosporin A

  • Sudhir Gupta
  • Takashi Tsuruo
  • Sastry Gollapudi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 323)

Abstract

The mdr 1 gene codes for a 170 kd P-glycoprotein (Pgp). The Pgp is a plasma membrane glycoprotein that shares extensive homology with numerous bacterial and eukaryotic transport proteins.1-3 The sequence encoding Pgp reveals a tandemly duplicated molecule of approximately 1280 amino acids. Each half consists of a large hydrophobic domain containing 6 putative membrane spanning ∝-helices and a highly conserved hydrophilic domain with an A TP binding site.4 P-glycoprotein has been implicated to play a major role in acquired multidrug resistance in cancer cells,6,6 in chloroquine-resistant Plasmodium falciparum infection,7,8 and possibly in human immunodeficiency virus 1 resistance to azidothymidine.9

Keywords

Cystic Fibrosis Transmembrane Conductance Regulator Phorbol Myristate Acetate Multidrug Resistant Gene Cytotoxic Molecule Cystic Fibrosis Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    P. Gros, J. Croop, and D. Housman, Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins, Cell 47:371 (1986).Google Scholar
  2. 2.
    C.-J. Chen, J.E. Chin, K. Ueda, D.P. Clark, I. Pastan, and M.M. Gottesman, Internal duplication and homology with bacterial transport proteins in the mdr 1 (P-glycoprotein) gene from multidrug resistant human cells, Cell 47:381 (1986).Google Scholar
  3. 3.
    J.H. Gerlach, J.A. Endicott, P.F. Juranka, G. Henderson, F. Sarangi, K.L. Deuchars, and V. Ling, Homology between P-glycoprotein and a bacterial hemolysin transport protein suggests a model for multidrug resistance, Nature 324:485 (1986).Google Scholar
  4. 4.
    M.M. Gottesman and I. Pastan, The multidrug transporter, a double-edge sword, J. Biol. Chem. 263:12163 (1988).Google Scholar
  5. 5.
    J.M. Croop, P. Gros, and D.E. Housman, Genetics of multidrug resistance, J. CUn. Invest. 81:1303, 1988.CrossRefGoogle Scholar
  6. 6.
    P.F. Juranka, R.L. Zastawny, and V. Ling, P-glycoprotein: multidrug resistance and a superfamily of membrane associated transport protein, FASEB J. 3:2583 (1989).Google Scholar
  7. 7.
    S.J. Foote, J.K. Thompson, A.F. Cowman, and D.J. Kemp, Amplification of the multidrug resistant gene in some chloroquine-resistant isolates of P. falciparum. Cell 57:921 (1989).Google Scholar
  8. 8.
    C.M. Wilson, A.E. Serrano, A. Wesley, M.P. Bogenschultz, A.H. Shanker, and D.F. Wirth, Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium /alciparum. Science 244:1184 (1989).Google Scholar
  9. 9.
    S. Gollapudi and S. Gupta, Human immunodeficiency virus-I (HIV-I)-induced P-glycoprotein expression, Biochem. Biophysic. Res. Commun. 171:1002, 1990.CrossRefGoogle Scholar
  10. 10.
    H. Hamada and T. Tsuruo, Functional role for the 170-180 kda glycoprotein specific to drug resistant tumor cells as treated by monoclonal antibodies, Proc. Natl. Acad. Sci. (USA) 83:7785 (1986).Google Scholar
  11. 11.
    S. Gupta, C.H. Kim, T. Tsuruo, and S. Gollapudi, Preferential expression of multidrug resistant gene 1 product (P-glycoprotein), a functionally active efflux pump, in human CD8+ T cells. A role in cytotoxic effector function, (submitted).Google Scholar
  12. 12.
    Y. Nishizuka, The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature 308:693 (1984).Google Scholar
  13. 13.
    S. Young, P. Parker, A. Ulrich, and S. Stable, Down regulation of protein kinase C is due to an increased rate of degradation, Biochem. J. 244:775 (1987).Google Scholar
  14. 14.
    R.J. Walker, V.A. Lazzaro, G.G. Duggin, J.S. Horvath, and D.J. Tiller. Cyclosporin A inhibits protein kinase C activity; a contributing mechanism in the development of nephrotoxicity. Biochem. Biophys. Res. Commun. 160:409 (1989).Google Scholar
  15. 15.
    W.F. Ng, F. Sarangi, R.L. Zastawny, V. Veinot-Drebot, and V. Ling, Identification of members of the P-glycoprotein multigene family, Mol. Cell. Biol. 9:1224 (1989).Google Scholar
  16. 16.
    K. Ueda, C. Cardarelli, M.M. Gottesman, and I. Pastan. Expression of a full length eDNA human MDR 1 gene confers resistance to colchicine, doxorubicin, and vinblastin, Proc. Natl. Acad. Sci. (USA) 84:3004, (1987).Google Scholar
  17. 17.
    P.G. Dabenham, N. Kartner, L. Siminovitch, J.R. Riordan, and V. Ling, DNA-mediated transfer of multiple drug resistance and plasma membrane glycoprotein expression, Mol. Cell. Biol. 2:881 (1982).Google Scholar
  18. 18.
    D. Shen, A. Fojo, I. Roninson, J. Chin, R. Soffir, I. Pastan, and M.M. Gottesman, Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr gene, Mol. Cell. Biol. 6:4039, (1986).Google Scholar
  19. 19.
    T. Thiebaut, T. Tsuruo, H. Hamada, M.M. Gottesman, I. Pastan, and M.C. Willingham, Cellular localization of multidrug resistant gene product P-glycoprotein in normal human tissues, Proc. Natl. Acad. Sci. (USA) 84:7734, (1987).Google Scholar
  20. 20.
    J.M. Croop, M. Raymond, D. Haber, A. Devault, R.J. Arceci, P. Gros, and D.E. Houseman, The mouse multidrug resistance (mdr) genes are expressed in a tissue specific manner in normal mouse tissues, Mol. Cell. Biol. 9:1346 (1989).Google Scholar
  21. 21.
    E. Georges, G. Bradley, J. Gariep, and V. Ling, Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies, Proc. Natl. Acad. Sci. (USA) 87:152 (1990).Google Scholar
  22. 22.
    C. Cordon-Cardo, J.P. O’Brien, J. Boccia, D. Casals, J.R. Bertino, and M.R. Melamed, Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor cells, J. Histochem. Cytochem. 28:1277 (1990).Google Scholar
  23. 23.
    I. Sugawara, I. Kataoka, Y. Morishita, H. Hamada, T. Tsuruo, S. Itoyama, and S. Mori, Tissue distribution of P-glycoprotein encoded by a multidrug resistant gene as revealed by a monoclonal antibody, MRKI6, Cancer Res. 48:1926, (1988).Google Scholar
  24. 24.
    K.E. Noonen, C. Beck, T.A. Holzmayer, J.E. Chin, J.S. Wunder, I.L. Andrulis, A.F. Gazdar, C.L. Willman, B. Griffith, D.D. Von Hoff, and I.B. Roninson, Quantitative analysis of MDR 1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction, Proc. Natl. Acad. Sci. (USA) 87:7160 (1990).Google Scholar
  25. 25.
    R. Pirker, L.J. Goldstein, H. Ludwig, W. Linkesh, C. Lechner, M.M. Gottesman, and I. Pastan, Expression of a multidrug resistant gene in blast crisis of chronic myelogenous leukemia, Cancer Commun. 1:141 (1989).Google Scholar
  26. 26.
    P.M. Chaudhary and I.B. Roninson, Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells, Cell 66:85 (1991).Google Scholar
  27. 27.
    J.R. Riordan, J.M. Rommens, B.-S. Kerem, N. Alon, R. Rozmahel, Z. Grzelczak, J. Zielenski, S. Lok, N. Plavsic, J. Chou, M.L. Drumm, M.C. Iannuzzi, F.S. Collins, L. Tsui, Identification of cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066 (1989).Google Scholar
  28. 28.
    M.P. Anderson, R.J. Gregory, S. Thompson, D.W. Souza, S. Paul, R.C. Mulligan, A.E. Smith, and M.J. Welsh, Demonstration of CFTR is a chloride channel by alteration of its ionic selectivity, Science 253:202 (1991).Google Scholar
  29. 29.
    J.K. Rubein, K.L. Kirk, T.A. Rado, and R.A. Frizzell, Cell cycle dependence of chloride permeability in normal and cystic fibrosis lymphocytes, Science 248:1416 (1990).Google Scholar
  30. 30.
    Y. Nishizuka, The molecular heterogeneity of protein kinase C and its implications for cellular regulation, Nature 334:661 (1988).Google Scholar
  31. 31.
    C.A. Koretzky, M. Wahi, M.E. Newton, and A. Weiss, Heterogeneity of protein kinase C isoenzyme gene expression in human T cell lines. Protein kinase Cβ is not required for certain functions, J. Immunol. 143:1692 (1989).Google Scholar
  32. 32.
    E.M. Shevach, The effect of cyclosporin A on the immune system, Ann. Rev. Immunol. 3:397 (1985).Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Sudhir Gupta
    • 1
  • Takashi Tsuruo
    • 2
  • Sastry Gollapudi
    • 1
  1. 1.Division of Basic and Clinical ImmunologyUniversity of CaliforniaIrvineUSA
  2. 2.Cancer Chemotherapy CenterJapanese Foundation for Cancer ResearchTokyo 170Japan

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