Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1989 Aug;63(8):3389–3398. doi: 10.1128/jvi.63.8.3389-3398.1989

Protein kinase activity associated with the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10).

T D Chung 1, J P Wymer 1, C C Smith 1, M Kulka 1, L Aurelian 1
PMCID: PMC250914  PMID: 2545912

Abstract

The large subunit of the herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (RR1) is demonstrated to possess serine/threonine-specific kinase activity. Computer-assisted sequence analysis identified regions within the amino terminus of ICP10 that are homologous to the catalytic domain of known protein kinases (PKs). An in vitro kinase assay confirmed the ability of ICP10, immunoprecipitated from either HSV-2-infected cells or from cells transfected with an ICP10 expression vector, to autophosphorylate and transphosphorylate exogenous substrates in the presence of ATP and Mg2+. The HSV-1 RR1 was shown to be negative for PK activity under these conditions. PK activity was localized to a 57-kDa amino-terminal region within ICP10 that lacked RR activity.

Full text

PDF
3389

Images in this article

3393Image
on p.3393
3393Image
on p.3393
3394Image
on p.3394
3394Image
on p.3394
3395Image
on p.3395
3395Image
on p.3395

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adkins B., Hunter T. Two structurally and functionally different forms of the transforming protein of PRC II avian sarcoma virus. Mol Cell Biol. 1982 Aug;2(8):890–896. doi: 10.1128/mcb.2.8.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson K. P., Frink R. J., Devi G. B., Gaylord B. H., Costa R. H., Wagner E. K. Detailed characterization of the mRNA mapping in the HindIII fragment K region of the herpes simplex virus type 1 genome. J Virol. 1981 Mar;37(3):1011–1027. doi: 10.1128/jvi.37.3.1011-1027.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aurelian L., Smith M. F., Cornish D. J. IgM antibody to a tumor-associated antigen (AG-4) induced by herpes simplex virus type 2: its use in location of the antigen in infected cells. J Natl Cancer Inst. 1976 Mar;56(3):471–477. doi: 10.1093/jnci/56.3.471. [DOI] [PubMed] [Google Scholar]
  4. Bacchetti S., Evelegh M. J., Muirhead B., Sartori C. S., Huszar D. Immunological characterization of herpes simplex virus type 1 and 2 polypeptide(s) involved in viral ribonucleotide reductase activity. J Virol. 1984 Feb;49(2):591–593. doi: 10.1128/jvi.49.2.591-593.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  6. Boss M. A., Dreyfuss G., Baltimore D. Localization of the Abelson murine leukemia virus protein in a detergent-insoluble subcellular matrix: architecture of the protein. J Virol. 1981 Nov;40(2):472–481. doi: 10.1128/jvi.40.2.472-481.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brenner S. Phosphotransferase sequence homology. Nature. 1987 Sep 3;329(6134):21–21. doi: 10.1038/329021a0. [DOI] [PubMed] [Google Scholar]
  8. Burr J. G., Dreyfuss G., Penman S., Buchanan J. M. Association of the src gene product of Rous sarcoma virus with cytoskeletal structures of chicken embryo fibroblasts. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3484–3488. doi: 10.1073/pnas.77.6.3484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Camacho A., Spear G. Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome. Cell. 1978 Nov;15(3):993–1002. doi: 10.1016/0092-8674(78)90283-0. [DOI] [PubMed] [Google Scholar]
  10. Flanders R. T., Kucera L. S., Raben M., Ricardo M. J., Jr Immunologic characterization of herpes simplex virus type 2 antigens ICP10 and ICSP11/12. Virus Res. 1985 Apr;2(3):245–260. doi: 10.1016/0168-1702(85)90012-7. [DOI] [PubMed] [Google Scholar]
  11. Frame M. C., Marsden H. S., Dutia B. M. The ribonucleotide reductase induced by herpes simplex virus type 1 involves minimally a complex of two polypeptides (136K and 38K). J Gen Virol. 1985 Jul;66(Pt 7):1581–1587. doi: 10.1099/0022-1317-66-7-1581. [DOI] [PubMed] [Google Scholar]
  12. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  13. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  14. Hayashi Y., Iwasaka T., Smith C. C., Aurelian L., Lewis G. K., Ts'o P. O. Multistep transformation by defined fragments of herpes simplex virus type 2 DNA: oncogenic region and its gene product. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8493–8497. doi: 10.1073/pnas.82.24.8493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hunter T. A thousand and one protein kinases. Cell. 1987 Sep 11;50(6):823–829. doi: 10.1016/0092-8674(87)90509-5. [DOI] [PubMed] [Google Scholar]
  16. Ingemarson R., Lankinen H. The herpes simplex virus type 1 ribonucleotide reductase is a tight complex of the type alpha 2 beta 2 composed of 40K and 140K proteins, of which the latter shows multiple forms due to proteolysis. Virology. 1987 Feb;156(2):417–422. doi: 10.1016/0042-6822(87)90422-3. [DOI] [PubMed] [Google Scholar]
  17. Iwasaka T., Smith C., Aurelian L., Ts'o P. O. The cervical tumor-associated antigen (ICP-10/AG-4) is encoded by the transforming region of the genome of herpes simplex virus type 2. Jpn J Cancer Res. 1985 Oct;76(10):946–958. [PubMed] [Google Scholar]
  18. Jariwalla R. J., Aurelian L., Ts'o P. O. Tumorigenic transformation induced by a specific fragment of DNA from herpes simplex virus type 2. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2279–2283. doi: 10.1073/pnas.77.4.2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jariwalla R. J., Tanczos B., Jones C., Ortiz J., Salimi-Lopez S. DNA amplification and neoplastic transformation mediated by a herpes simplex DNA fragment containing cell-related sequences. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1738–1742. doi: 10.1073/pnas.83.6.1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones C., Ortiz J., Jariwalla R. J. Localization and comparative nucleotide sequence analysis of the transforming domain in herpes simplex virus DNA containing repetitive genetic elements. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7855–7859. doi: 10.1073/pnas.83.20.7855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kamps M. P., Sefton B. M. Neither arginine nor histidine can carry out the function of lysine-295 in the ATP-binding site of p60src. Mol Cell Biol. 1986 Mar;6(3):751–757. doi: 10.1128/mcb.6.3.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kamps M. P., Taylor S. S., Sefton B. M. Direct evidence that oncogenic tyrosine kinases and cyclic AMP-dependent protein kinase have homologous ATP-binding sites. Nature. 1984 Aug 16;310(5978):589–592. doi: 10.1038/310589a0. [DOI] [PubMed] [Google Scholar]
  23. Krueger J. G., Garber E. A., Goldberg A. R. Subcellular localization of pp60src in RSV-transformed cells. Curr Top Microbiol Immunol. 1983;107:51–124. [PubMed] [Google Scholar]
  24. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  25. Langelier Y., Buttin G. Characterization of ribonucleotide reductase induction in BHK-21/C13 Syrian hamster cell line upon infection by herpes simplex virus (HSV). J Gen Virol. 1981 Nov;57(Pt 1):21–31. doi: 10.1099/0022-1317-57-1-21. [DOI] [PubMed] [Google Scholar]
  26. Lankinen H., Gräslund A., Thelander L. Induction of a new ribonucleotide reductase after infection of mouse L cells with pseudorabies virus. J Virol. 1982 Mar;41(3):893–900. doi: 10.1128/jvi.41.3.893-900.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lemaster S., Roizman B. Herpes simplex virus phosphoproteins. II. Characterization of the virion protein kinase and of the polypeptides phosphorylated in the virion. J Virol. 1980 Sep;35(3):798–811. doi: 10.1128/jvi.35.3.798-811.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Manger R., Rasheed S., Rohrschneider L. Localization of the feline sarcoma virus fgr gene product (P70gag-actin-fgr): association with the plasma membrane and detergent-insoluble matrix. J Virol. 1986 Jul;59(1):66–72. doi: 10.1128/jvi.59.1.66-72.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McGeoch D. J., Moss H. W., McNab D., Frame M. C. DNA sequence and genetic content of the HindIII l region in the short unique component of the herpes simplex virus type 2 genome: identification of the gene encoding glycoprotein G, and evolutionary comparisons. J Gen Virol. 1987 Jan;68(Pt 1):19–38. doi: 10.1099/0022-1317-68-1-19. [DOI] [PubMed] [Google Scholar]
  30. McLauchlan J., Clements J. B. Organization of the herpes simplex virus type 1 transcription unit encoding two early proteins with molecular weights of 140000 and 40000. J Gen Virol. 1983 May;64(Pt 5):997–1006. doi: 10.1099/0022-1317-64-5-997. [DOI] [PubMed] [Google Scholar]
  31. Meignier B., Longnecker R., Mavromara-Nazos P., Sears A. E., Roizman B. Virulence of and establishment of latency by genetically engineered deletion mutants of herpes simplex virus 1. Virology. 1988 Jan;162(1):251–254. doi: 10.1016/0042-6822(88)90417-5. [DOI] [PubMed] [Google Scholar]
  32. Moelling K., Heimann B., Beimling P., Rapp U. R., Sander T. Serine- and threonine-specific protein kinase activities of purified gag-mil and gag-raf proteins. Nature. 1984 Dec 6;312(5994):558–561. doi: 10.1038/312558a0. [DOI] [PubMed] [Google Scholar]
  33. Mohana Rao J. K., Argos P. A conformational preference parameter to predict helices in integral membrane proteins. Biochim Biophys Acta. 1986 Jan 30;869(2):197–214. doi: 10.1016/0167-4838(86)90295-5. [DOI] [PubMed] [Google Scholar]
  34. Nikas I., McLauchlan J., Davison A. J., Taylor W. R., Clements J. B. Structural features of ribonucleotide reductase. Proteins. 1986 Dec;1(4):376–384. doi: 10.1002/prot.340010411. [DOI] [PubMed] [Google Scholar]
  35. Parker R. C., Varmus H. E., Bishop J. M. Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src. Cell. 1984 May;37(1):131–139. doi: 10.1016/0092-8674(84)90308-8. [DOI] [PubMed] [Google Scholar]
  36. Perlman D., Halvorson H. O. A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides. J Mol Biol. 1983 Jun 25;167(2):391–409. doi: 10.1016/s0022-2836(83)80341-6. [DOI] [PubMed] [Google Scholar]
  37. Prywes R., Foulkes J. G., Rosenberg N., Baltimore D. Sequences of the A-MuLV protein needed for fibroblast and lymphoid cell transformation. Cell. 1983 Sep;34(2):569–579. doi: 10.1016/0092-8674(83)90389-6. [DOI] [PubMed] [Google Scholar]
  38. Purves F. C., Longnecker R. M., Leader D. P., Roizman B. Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture. J Virol. 1987 Sep;61(9):2896–2901. doi: 10.1128/jvi.61.9.2896-2901.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Raptis L., Lamfrom H., Benjamin T. L. Regulation of cellular phenotype and expression of polyomavirus middle T antigen in rat fibroblasts. Mol Cell Biol. 1985 Sep;5(9):2476–2486. doi: 10.1128/mcb.5.9.2476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Roberts M. S., Boundy A., O'Hare P., Pizzorno M. C., Ciufo D. M., Hayward G. S. Direct correlation between a negative autoregulatory response element at the cap site of the herpes simplex virus type 1 IE175 (alpha 4) promoter and a specific binding site for the IE175 (ICP4) protein. J Virol. 1988 Nov;62(11):4307–4320. doi: 10.1128/jvi.62.11.4307-4320.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  42. Sefton B. M., Hunter T., Beemon K., Eckhart W. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell. 1980 Jul;20(3):807–816. doi: 10.1016/0092-8674(80)90327-x. [DOI] [PubMed] [Google Scholar]
  43. Showalter S. D., Zweig M., Hampar B. Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP 4. Infect Immun. 1981 Dec;34(3):684–692. doi: 10.1128/iai.34.3.684-692.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Smith R. F., Smith T. F. Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus. J Virol. 1989 Jan;63(1):450–455. doi: 10.1128/jvi.63.1.450-455.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Strnad B. C., Aurelian L. Proteins of herpesvirus type 2. III. Isolation and immunologic characterization of a large molecular weight viral protein. Virology. 1978 Jun 15;87(2):401–415. doi: 10.1016/0042-6822(78)90144-7. [DOI] [PubMed] [Google Scholar]
  46. Swain M. A., Galloway D. A. Herpes simplex virus specifies two subunits of ribonucleotide reductase encoded by 3'-coterminal transcripts. J Virol. 1986 Mar;57(3):802–808. doi: 10.1128/jvi.57.3.802-808.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Thelander L., Reichard P. Reduction of ribonucleotides. Annu Rev Biochem. 1979;48:133–158. doi: 10.1146/annurev.bi.48.070179.001025. [DOI] [PubMed] [Google Scholar]
  48. Thom D., Powell A. J., Lloyd C. W., Rees D. A. Rapid isolation of plasma membranes in high yield from cultured fibroblasts. Biochem J. 1977 Nov 15;168(2):187–194. doi: 10.1042/bj1680187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wierenga R. K., Hol W. G. Predicted nucleotide-binding properties of p21 protein and its cancer-associated variant. Nature. 1983 Apr 28;302(5911):842–844. doi: 10.1038/302842a0. [DOI] [PubMed] [Google Scholar]
  50. Wilcox K. W., Kohn A., Sklyanskaya E., Roizman B. Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA. J Virol. 1980 Jan;33(1):167–182. doi: 10.1128/jvi.33.1.167-182.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wymer J. P., Chung T. D., Chang Y. N., Hayward G. S., Aurelian L. Identification of immediate-early-type cis-response elements in the promoter for the ribonucleotide reductase large subunit from herpes simplex virus type 2. J Virol. 1989 Jun;63(6):2773–2784. doi: 10.1128/jvi.63.6.2773-2784.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES