Display options
Cite
Druker BJ, Sibert L, Roberts TM. Polyomavirus middle T-antigen NPTY mutants. J Virol. 1992;66(10):5770-6doi: 10.1128/JVI.66.10.5770-5776.1992.
Druker, B. J., Sibert, L., & Roberts, T. M. (1992). Polyomavirus middle T-antigen NPTY mutants. Journal of virology, 66(10), 5770-6. https://doi.org/10.1128/JVI.66.10.5770-5776.1992
Druker, B J, et al. "Polyomavirus middle T-antigen NPTY mutants." Journal of virology vol. 66,10 (1992): 5770-6. doi: https://doi.org/10.1128/JVI.66.10.5770-5776.1992
Druker BJ, Sibert L, Roberts TM. Polyomavirus middle T-antigen NPTY mutants. J Virol. 1992 Oct;66(10):5770-6. doi: 10.1128/JVI.66.10.5770-5776.1992. PMID: 1326642; PMCID: PMC241452.
Copy Download .nbib Format: NLM
Share it on
Full text links
Atypon Free PMC Article

J Virol. 1992 Oct;66(10):5770-6. doi: 10.1128/JVI.66.10.5770-5776.1992.

Polyomavirus middle T-antigen NPTY mutants.

Journal of virology

B J Druker, L Sibert, T M Roberts

Affiliations

  1. Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.

PMID: 1326642 PMCID: PMC241452 DOI: 10.1128/JVI.66.10.5770-5776.1992
Free PMC Article

Abstract

A polyomavirus middle T-antigen (MTAg) mutant containing a substitution of Leu for Pro at amino acid 248 has previously been described as completely transformation defective (B. J. Druker, L. Ling, B. Cohen, T. M. Roberts, and B. S. Schaffhausen, J. Virol. 64:4454-4461, 1990). This mutant had no alterations in associated proteins or associated kinase activities compared with wild-type MTAg. Pro-248 lies in a tetrameric sequence, NPTY, which is reminiscent of the so-called NPXY sequence in the low-density-lipoprotein receptor. In the low-density-lipoprotein receptor, mutations in the NPXY motif but not in the surrounding amino acids abolish receptor function, apparently by decreasing receptor internalization (W. Chen, J. L. Goldstein, and M. S. Brown, J. Biol. Chem. 265:3116-3123, 1990). To determine whether this sequence represents a functional motif in MTAg as well, a series of single amino acid substitutions was constructed in this region of MTAg. All of the mutations of N, P, T, or Y, including the relatively conservative substitution of Ser for Thr at amino acid 249, resulted in a transformation-defective MTAg, whereas mutations outside of this sequence allowed mutants to retain near-wild-type transformation capabilities. Transformation-defective mutants with mutations in the NPTY region behaved similarly to the mutant with the original Pro-248-to-Leu-248 mutation when assayed for associated proteins and activities in vitro; that is, they retained a full complement of wild-type activities and associated proteins. Further, insertion of the tetrameric sequence NPTY downstream of the mutated motif restored transforming abilities to these mutants. Thus, the tetrameric sequence NPTY in MTAg appears to represent a well-defined functional motif of MTAg.

Similar articles

Cited by

References

  1. Cell. 1991 Dec 20;67(6):1203-9 - PubMed
  2. Nucleic Acids Res. 1991 Dec 25;19(24):6855-61 - PubMed
  3. J Virol. 1990 Sep;64(9):4454-61 - PubMed
  4. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3624-8 - PubMed
  5. Cell. 1987 Sep 25;50(7):1031-7 - PubMed
  6. Mol Cell Biol. 1988 Jan;8(1):176-85 - PubMed
  7. J Virol. 1988 Sep;62(9):3407-14 - PubMed
  8. J Virol. 1985 Dec;56(3):1023-6 - PubMed
  9. J Virol. 1986 Dec;60(3):1075-84 - PubMed
  10. Nature. 1987 Jan 8-14;325(7000):171-3 - PubMed
  11. Biochim Biophys Acta. 1987 Nov 25;907(3):299-321 - PubMed
  12. Cell. 1984 Oct;38(3):767-77 - PubMed
  13. Nature. 1983 Jun 2-8;303(5916):435-9 - PubMed
  14. J Virol. 1980 Jul;35(1):219-32 - PubMed
  15. J Virol. 1981 Oct;40(1):184-96 - PubMed
  16. Nature. 1984 Apr 19-25;308(5961):748-50 - PubMed
  17. J Virol. 1979 Sep;31(3):645-56 - PubMed
  18. J Virol. 1992 Mar;66(3):1702-8 - PubMed
  19. Cell. 1991 Dec 20;67(6):1195-201 - PubMed
  20. Cell. 1991 Jan 25;64(2):281-302 - PubMed
  21. J Biol Chem. 1990 Feb 25;265(6):3116-23 - PubMed
  22. Cell. 1990 Jan 12;60(1):167-76 - PubMed
  23. EMBO J. 1985 Jun;4(6):1471-7 - PubMed
  24. J Virol. 1986 Jul;59(1):82-9 - PubMed
  25. J Virol. 1986 Aug;59(2):384-91 - PubMed
  26. J Virol. 1987 Oct;61(10):3299-305 - PubMed
  27. EMBO J. 1988 Dec 1;7(12):3845-55 - PubMed
  28. Biochem J. 1987 Oct 1;247(1):165-74 - PubMed
  29. Nature. 1985 May 16-22;315(6016):239-42 - PubMed
  30. Nucleic Acids Res. 1985 Dec 20;13(24):8765-85 - PubMed
  31. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4307-11 - PubMed
  32. Mol Cell Biol. 1986 May;6(5):1545-51 - PubMed
  33. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2150-4 - PubMed
  34. Proc Natl Acad Sci U S A. 1970 Sep;67(1):394-9 - PubMed
  35. Nature. 1970 Aug 15;227(5259):680-5 - PubMed
  36. Mol Cell Biol. 1984 Dec;4(12):2774-83 - PubMed
  37. Nature. 1980 Jan 31;283(5746):445-53 - PubMed
  38. Nature. 1981 Aug 13;292(5824):595-600 - PubMed
  39. Nature. 1982 Dec 23;300(5894):713-8 - PubMed
  40. EMBO J. 1984 Mar;3(3):585-91 - PubMed
  41. Cell. 1984 Jul;37(3):1053-62 - PubMed
  42. Proc Natl Acad Sci U S A. 1978 Jan;75(1):79-83 - PubMed
  43. J Cell Biol. 1990 Oct;111(4):1393-407 - PubMed

Substances

MeSH terms

Publication Types

Grant support

LinkOut - more resources