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. 1995 May 1;181(5):1899–1904. doi: 10.1084/jem.181.5.1899

Proteolytic processing is required for viral superantigen activity

PMCID: PMC2192000  PMID: 7722465

Abstract

The mouse mammary tumor virus-7 superantigen (vSAG7) is proteolytically processed in B cells at as many as three positions. Proteolytic processing appears to be important for superantigen activity because a processed form of vSAG7 was predominant among those forms that were found to bind to major histocompatibility complex class II molecules. To determine the functional significance of proteolytic processing, a mutation was introduced in vSAG7 at one of the sites where proteolytic cleavage is thought to take place in B cells. Elimination of the putative processing site at position 171 abrogated detectable vSAG7 surface expression in B cells, indicating that proteolytic processing is required for vSAG7 function. Coexpression in insect cells of vSAG7 and furin, a proprotein-processing enzyme, also demonstrated that furin could process vSAG7 at position 171.

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Selected References

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  1. Arnold L. W., LoCascio N. J., Lutz P. M., Pennell C. A., Klapper D., Haughton G. Antigen-induced lymphomagenesis: identification of a murine B cell lymphoma with known antigen specificity. J Immunol. 1983 Oct;131(4):2064–2068. [PubMed] [Google Scholar]
  2. Barr P. J. Mammalian subtilisins: the long-sought dibasic processing endoproteases. Cell. 1991 Jul 12;66(1):1–3. doi: 10.1016/0092-8674(91)90129-m. [DOI] [PubMed] [Google Scholar]
  3. Choi Y. W., Herman A., DiGiusto D., Wade T., Marrack P., Kappler J. Residues of the variable region of the T-cell-receptor beta-chain that interact with S. aureus toxin superantigens. Nature. 1990 Aug 2;346(6283):471–473. doi: 10.1038/346471a0. [DOI] [PubMed] [Google Scholar]
  4. Dong J. Y., Dubay J. W., Perez L. G., Hunter E. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein define a requirement for dibasic residues for intracellular cleavage. J Virol. 1992 Feb;66(2):865–874. doi: 10.1128/jvi.66.2.865-874.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H. D., Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992 Nov 26;360(6402):358–361. doi: 10.1038/360358a0. [DOI] [PubMed] [Google Scholar]
  7. Hatsuzawa K., Hosaka M., Nakagawa T., Nagase M., Shoda A., Murakami K., Nakayama K. Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cells. J Biol Chem. 1990 Dec 25;265(36):22075–22078. [PubMed] [Google Scholar]
  8. Klenk H. D., Rott R. The molecular biology of influenza virus pathogenicity. Adv Virus Res. 1988;34:247–281. doi: 10.1016/S0065-3527(08)60520-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kolodziej P. A., Young R. A. Epitope tagging and protein surveillance. Methods Enzymol. 1991;194:508–519. doi: 10.1016/0076-6879(91)94038-e. [DOI] [PubMed] [Google Scholar]
  10. Kotzin B. L., Leung D. Y., Kappler J., Marrack P. Superantigens and their potential role in human disease. Adv Immunol. 1993;54:99–166. doi: 10.1016/s0065-2776(08)60534-9. [DOI] [PubMed] [Google Scholar]
  11. Kozono H., White J., Clements J., Marrack P., Kappler J. Production of soluble MHC class II proteins with covalently bound single peptides. Nature. 1994 May 12;369(6476):151–154. doi: 10.1038/369151a0. [DOI] [PubMed] [Google Scholar]
  12. Leduc R., Molloy S. S., Thorne B. A., Thomas G. Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage. J Biol Chem. 1992 Jul 15;267(20):14304–14308. [PubMed] [Google Scholar]
  13. McCune J. M., Rabin L. B., Feinberg M. B., Lieberman M., Kosek J. C., Reyes G. R., Weissman I. L. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988 Apr 8;53(1):55–67. doi: 10.1016/0092-8674(88)90487-4. [DOI] [PubMed] [Google Scholar]
  14. Molloy S. S., Thomas L., VanSlyke J. K., Stenberg P. E., Thomas G. Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface. EMBO J. 1994 Jan 1;13(1):18–33. doi: 10.1002/j.1460-2075.1994.tb06231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rehemtulla A., Kaufman R. J. Preferred sequence requirements for cleavage of pro-von Willebrand factor by propeptide-processing enzymes. Blood. 1992 May 1;79(9):2349–2355. [PubMed] [Google Scholar]
  16. Schalken J. A., Roebroek A. J., Oomen P. P., Wagenaar S. S., Debruyne F. M., Bloemers H. P., Van de Ven W. J. fur gene expression as a discriminating marker for small cell and nonsmall cell lung carcinomas. J Clin Invest. 1987 Dec;80(6):1545–1549. doi: 10.1172/JCI113240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Scherer M. T., Ignatowicz L., Winslow G. M., Kappler J. W., Marrack P. Superantigens: bacterial and viral proteins that manipulate the immune system. Annu Rev Cell Biol. 1993;9:101–128. doi: 10.1146/annurev.cb.09.110193.000533. [DOI] [PubMed] [Google Scholar]
  18. Seidah N. G., Marcinkiewicz M., Benjannet S., Gaspar L., Beaubien G., Mattei M. G., Lazure C., Mbikay M., Chrétien M. Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2. Mol Endocrinol. 1991 Jan;5(1):111–122. doi: 10.1210/mend-5-1-111. [DOI] [PubMed] [Google Scholar]
  19. Smeekens S. P., Avruch A. S., LaMendola J., Chan S. J., Steiner D. F. Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):340–344. doi: 10.1073/pnas.88.2.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Steiner D. F., Smeekens S. P., Ohagi S., Chan S. J. The new enzymology of precursor processing endoproteases. J Biol Chem. 1992 Nov 25;267(33):23435–23438. [PubMed] [Google Scholar]
  21. Vidricaire G., Denault J. B., Leduc R. Characterization of a secreted form of human furin endoprotease. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1011–1018. doi: 10.1006/bbrc.1993.2145. [DOI] [PubMed] [Google Scholar]
  22. Wells D. E., Compans R. W. Expression and characterization of a functional human immunodeficiency virus envelope glycoprotein in insect cells. Virology. 1990 Jun;176(2):575–586. doi: 10.1016/0042-6822(90)90028-p. [DOI] [PubMed] [Google Scholar]
  23. Winslow G. M., Marrack P., Kappler J. W. Processing and major histocompatibility complex binding of the MTV7 superantigen. Immunity. 1994 Apr;1(1):23–33. doi: 10.1016/1074-7613(94)90006-x. [DOI] [PubMed] [Google Scholar]
  24. Winslow G. M., Scherer M. T., Kappler J. W., Marrack P. Detection and biochemical characterization of the mouse mammary tumor virus 7 superantigen (Mls-1a). Cell. 1992 Nov 27;71(5):719–730. doi: 10.1016/0092-8674(92)90549-r. [DOI] [PubMed] [Google Scholar]
  25. Yazdanbakhsh K., Park C. G., Winslow G. M., Choi Y. Direct evidence for the role of COOH terminus of mouse mammary tumor virus superantigen in determining T cell receptor V beta specificity. J Exp Med. 1993 Aug 1;178(2):737–741. doi: 10.1084/jem.178.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]

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