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. 1997 Apr;71(4):2615–2620. doi: 10.1128/jvi.71.4.2615-2620.1997

The murine AIDS virus Gag precursor protein binds to the SH3 domain of c-Abl.

P Dupraz 1, N Rebai 1, S J Klein 1, N Beaulieu 1, P Jolicoeur 1
PMCID: PMC191382  PMID: 9060613

Abstract

The Pr60gag protein of the murine AIDS (MAIDS) defective virus promotes the proliferation of the infected target B cells and is responsible for inducing a severe immunodeficiency disease. Using the yeast two-hybrid system, we identified the SH3 domain of c-Abl as interacting with the proline-rich p12 domain of Pr60gag. The two proteins were shown to associate in vitro and in vivo in MAIDS virus-infected B cells. Overexpression of Pr60(gag) in these cells led to a detectable increase of the levels of c-Abl protein and to its translocation at the membrane. These results suggest that this viral protein serves as a docking site for signaling molecules and that c-Abl may be involved in the proliferation of infected B cells.

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Selected References

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  1. Alexandropoulos K., Cheng G., Baltimore D. Proline-rich sequences that bind to Src homology 3 domains with individual specificities. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3110–3114. doi: 10.1073/pnas.92.8.3110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aziz D. C., Hanna Z., Jolicoeur P. Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature. 1989 Apr 6;338(6215):505–508. doi: 10.1038/338505a0. [DOI] [PubMed] [Google Scholar]
  3. Breeden L., Nasmyth K. Regulation of the yeast HO gene. Cold Spring Harb Symp Quant Biol. 1985;50:643–650. doi: 10.1101/sqb.1985.050.01.078. [DOI] [PubMed] [Google Scholar]
  4. Chattopadhyay S. K., Morse H. C., 3rd, Makino M., Ruscetti S. K., Hartley J. W. Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1989 May;86(10):3862–3866. doi: 10.1073/pnas.86.10.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesebro B., Britt W., Evans L., Wehrly K., Nishio J., Cloyd M. Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of friend MCF and Friend ecotropic murine leukemia virus. Virology. 1983 May;127(1):134–148. doi: 10.1016/0042-6822(83)90378-1. [DOI] [PubMed] [Google Scholar]
  6. Cicchetti P., Mayer B. J., Thiel G., Baltimore D. Identification of a protein that binds to the SH3 region of Abl and is similar to Bcr and GAP-rho. Science. 1992 Aug 7;257(5071):803–806. doi: 10.1126/science.1379745. [DOI] [PubMed] [Google Scholar]
  7. Dai Z., Pendergast A. M. Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity. Genes Dev. 1995 Nov 1;9(21):2569–2582. doi: 10.1101/gad.9.21.2569. [DOI] [PubMed] [Google Scholar]
  8. Daley G. Q., Van Etten R. A., Jackson P. K., Bernards A., Baltimore D. Nonmyristoylated Abl proteins transform a factor-dependent hematopoietic cell line. Mol Cell Biol. 1992 Apr;12(4):1864–1871. doi: 10.1128/mcb.12.4.1864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Daniel R., Wong P. M., Chung S. W. Isoform-specific functions of c-abl: type I is necessary for differentiation, and type IV is inhibitory to apoptosis. Cell Growth Differ. 1996 Sep;7(9):1141–1148. [PubMed] [Google Scholar]
  10. Doyon L., Simard C., Sékaly R. P., Jolicoeur P. Evidence that the murine AIDS defective virus does not encode a superantigen. J Virol. 1996 Jan;70(1):1–9. doi: 10.1128/jvi.70.1.1-9.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feller S. M., Knudsen B., Hanafusa H. c-Abl kinase regulates the protein binding activity of c-Crk. EMBO J. 1994 May 15;13(10):2341–2351. doi: 10.1002/j.1460-2075.1994.tb06518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fields S., Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. doi: 10.1038/340245a0. [DOI] [PubMed] [Google Scholar]
  13. Franz W. M., Berger P., Wang J. Y. Deletion of an N-terminal regulatory domain of the c-abl tyrosine kinase activates its oncogenic potential. EMBO J. 1989 Jan;8(1):137–147. doi: 10.1002/j.1460-2075.1989.tb03358.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huang M., Hanna Z., Jolicoeur P. Mutational analysis of the murine AIDS-defective viral genome reveals a high reversion rate in vivo and a requirement for an intact Pr60gag protein for efficient induction of disease. J Virol. 1995 Jan;69(1):60–68. doi: 10.1128/jvi.69.1.60-68.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huang M., Jolicoeur P. Characterization of the gag/fusion protein encoded by the defective Duplan retrovirus inducing murine acquired immunodeficiency syndrome. J Virol. 1990 Dec;64(12):5764–5772. doi: 10.1128/jvi.64.12.5764-5772.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huang M., Jolicoeur P. Myristylation of Pr60gag of the murine AIDS-defective virus is required to induce disease and notably for the expansion of its target cells. J Virol. 1994 Sep;68(9):5648–5655. doi: 10.1128/jvi.68.9.5648-5655.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Huang M., Simard C., Kay D. G., Jolicoeur P. The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage. J Virol. 1991 Dec;65(12):6562–6571. doi: 10.1128/jvi.65.12.6562-6571.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jackson P., Baltimore D. N-terminal mutations activate the leukemogenic potential of the myristoylated form of c-abl. EMBO J. 1989 Feb;8(2):449–456. doi: 10.1002/j.1460-2075.1989.tb03397.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jolicoeur P. Murine acquired immunodeficiency syndrome (MAIDS): an animal model to study the AIDS pathogenesis. FASEB J. 1991 Jul;5(10):2398–2405. doi: 10.1096/fasebj.5.10.2065888. [DOI] [PubMed] [Google Scholar]
  20. Kubo Y., Kakimi K., Higo K., Wang L., Kobayashi H., Kuribayashi K., Masuda T., Hirama T., Ishimoto A. The p15gag and p12gag regions are both necessary for the pathogenicity of the murine AIDS virus. J Virol. 1994 Sep;68(9):5532–5537. doi: 10.1128/jvi.68.9.5532-5537.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Luban J., Alin K. B., Bossolt K. L., Humaran T., Goff S. P. Genetic assay for multimerization of retroviral gag polyproteins. J Virol. 1992 Aug;66(8):5157–5160. doi: 10.1128/jvi.66.8.5157-5160.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mayer B. J., Jackson P. K., Baltimore D. The noncatalytic src homology region 2 segment of abl tyrosine kinase binds to tyrosine-phosphorylated cellular proteins with high affinity. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):627–631. doi: 10.1073/pnas.88.2.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morse H. C., 3rd, Chattopadhyay S. K., Makino M., Fredrickson T. N., Hügin A. W., Hartley J. W. Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS. AIDS. 1992 Jul;6(7):607–621. doi: 10.1097/00002030-199207000-00001. [DOI] [PubMed] [Google Scholar]
  24. Pendergast A. M., Muller A. J., Havlik M. H., Clark R., McCormick F., Witte O. N. Evidence for regulation of the human ABL tyrosine kinase by a cellular inhibitor. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5927–5931. doi: 10.1073/pnas.88.13.5927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pozsgay J. M., Beilharz M. W., Wines B. D., Hess A. D., Pitha P. M. The MA (p15) and p12 regions of the gag gene are sufficient for the pathogenicity of the murine AIDS virus. J Virol. 1993 Oct;67(10):5989–5999. doi: 10.1128/jvi.67.10.5989-5999.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rassart E., Shang M., Boie Y., Jolicoeur P. Studies on emerging radiation leukemia virus variants in C57BL/Ka mice. J Virol. 1986 Apr;58(1):96–106. doi: 10.1128/jvi.58.1.96-106.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ren R., Mayer B. J., Cicchetti P., Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science. 1993 Feb 19;259(5098):1157–1161. doi: 10.1126/science.8438166. [DOI] [PubMed] [Google Scholar]
  28. Rivero-Lezcano O. M., Marcilla A., Sameshima J. H., Robbins K. C. Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. Mol Cell Biol. 1995 Oct;15(10):5725–5731. doi: 10.1128/mcb.15.10.5725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rosenberg N., Baltimore D., Scher C. D. In vitro transformation of lymphoid cells by Abelson murine leukemia virus. Proc Natl Acad Sci U S A. 1975 May;72(5):1932–1936. doi: 10.1073/pnas.72.5.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rosenberg N., Witte O. N. The viral and cellular forms of the Abelson (abl) oncogene. Adv Virus Res. 1988;35:39–81. doi: 10.1016/s0065-3527(08)60708-3. [DOI] [PubMed] [Google Scholar]
  31. Rosti V., Bergamaschi G., Lucotti C., Danova M., Carlo-Stella C., Locatelli F., Tonon L., Mazzini G., Cazzola M. Oligodeoxynucleotides antisense to c-abl specifically inhibit entry into S-phase of CD34+ hematopoietic cells and their differentiation to granulocyte-macrophage progenitors. Blood. 1995 Nov 1;86(9):3387–3393. [PubMed] [Google Scholar]
  32. Saksela K., Cheng G., Baltimore D. Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4. EMBO J. 1995 Feb 1;14(3):484–491. doi: 10.1002/j.1460-2075.1995.tb07024.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sawyers C. L., McLaughlin J., Goga A., Havlik M., Witte O. The nuclear tyrosine kinase c-Abl negatively regulates cell growth. Cell. 1994 Apr 8;77(1):121–131. doi: 10.1016/0092-8674(94)90240-2. [DOI] [PubMed] [Google Scholar]
  34. Schiestl R. H., Gietz R. D. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr Genet. 1989 Dec;16(5-6):339–346. doi: 10.1007/BF00340712. [DOI] [PubMed] [Google Scholar]
  35. Schiff-Maker L., Burns M. C., Konopka J. B., Clark S., Witte O. N., Rosenberg N. Monoclonal antibodies specific for v-abl- and c-abl-encoded molecules. J Virol. 1986 Mar;57(3):1182–1186. doi: 10.1128/jvi.57.3.1182-1186.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shi Y., Alin K., Goff S. P. Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. Genes Dev. 1995 Nov 1;9(21):2583–2597. doi: 10.1101/gad.9.21.2583. [DOI] [PubMed] [Google Scholar]
  37. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  38. Van Etten R. A., Debnath J., Zhou H., Casasnovas J. M. Introduction of a loss-of-function point mutation from the SH3 region of the Caenorhabditis elegans sem-5 gene activates the transforming ability of c-abl in vivo and abolishes binding of proline-rich ligands in vitro. Oncogene. 1995 May 18;10(10):1977–1988. [PubMed] [Google Scholar]
  39. Van Etten R. A., Jackson P., Baltimore D. The mouse type IV c-abl gene product is a nuclear protein, and activation of transforming ability is associated with cytoplasmic localization. Cell. 1989 Aug 25;58(4):669–678. doi: 10.1016/0092-8674(89)90102-5. [DOI] [PubMed] [Google Scholar]
  40. Vojtek A. B., Hollenberg S. M., Cooper J. A. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 1993 Jul 16;74(1):205–214. doi: 10.1016/0092-8674(93)90307-c. [DOI] [PubMed] [Google Scholar]
  41. Wen S. T., Jackson P. K., Van Etten R. A. The cytostatic function of c-Abl is controlled by multiple nuclear localization signals and requires the p53 and Rb tumor suppressor gene products. EMBO J. 1996 Apr 1;15(7):1583–1595. [PMC free article] [PubMed] [Google Scholar]
  42. Wetzler M., Talpaz M., Van Etten R. A., Hirsh-Ginsberg C., Beran M., Kurzrock R. Subcellular localization of Bcr, Abl, and Bcr-Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiation. J Clin Invest. 1993 Oct;92(4):1925–1939. doi: 10.1172/JCI116786. [DOI] [PMC free article] [PubMed] [Google Scholar]

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