Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 Sep 1;182(3):865–874. doi: 10.1084/jem.182.3.865

Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis

PMCID: PMC2192163  PMID: 7544399

Abstract

We have identified a serine/threonine kinase that is rapidly activated during Fas-mediated apoptosis. Fas-activated serine/threonine kinase (FAST) is phosphorylated on serine and threonine residues in Jurkat cells. In response to Fas ligation, it is rapidly dephosphorylated and concomitantly activated to phosphorylate TIA-1, a nuclear RNA-binding protein that has been implicated as an effector of apoptosis. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation, suggesting a role in signaling downstream events in the apoptotic program. Our results introduce Fast and TIA-1 as components of a molecular cascade involved in signaling Fas-mediated apoptosis.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

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

  1. Alnemri E. S., Fernandes-Alnemri T., Litwack G. Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. J Biol Chem. 1995 Mar 3;270(9):4312–4317. doi: 10.1074/jbc.270.9.4312. [DOI] [PubMed] [Google Scholar]
  2. Anderson P., Nagler-Anderson C., O'Brien C., Levine H., Watkins S., Slayter H. S., Blue M. L., Schlossman S. F. A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes. J Immunol. 1990 Jan 15;144(2):574–582. [PubMed] [Google Scholar]
  3. Chien C. T., Bartel P. L., Sternglanz R., Fields S. The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9578–9582. doi: 10.1073/pnas.88.21.9578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chung T. D., Wymer J. P., Smith C. C., Kulka M., Aurelian L. Protein kinase activity associated with the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10). J Virol. 1989 Aug;63(8):3389–3398. doi: 10.1128/jvi.63.8.3389-3398.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cifone M. G., De Maria R., Roncaioli P., Rippo M. R., Azuma M., Lanier L. L., Santoni A., Testi R. Apoptotic signaling through CD95 (Fas/Apo-1) activates an acidic sphingomyelinase. J Exp Med. 1994 Oct 1;180(4):1547–1552. doi: 10.1084/jem.180.4.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen J. J. Apoptosis. Immunol Today. 1993 Mar;14(3):126–130. doi: 10.1016/0167-5699(93)90214-6. [DOI] [PubMed] [Google Scholar]
  7. Dhein J., Walczak H., Bäumler C., Debatin K. M., Krammer P. H. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995 Feb 2;373(6513):438–441. doi: 10.1038/373438a0. [DOI] [PubMed] [Google Scholar]
  8. Dobrowsky R. T., Kamibayashi C., Mumby M. C., Hannun Y. A. Ceramide activates heterotrimeric protein phosphatase 2A. J Biol Chem. 1993 Jul 25;268(21):15523–15530. [PubMed] [Google Scholar]
  9. Durfee T., Becherer K., Chen P. L., Yeh S. H., Yang Y., Kilburn A. E., Lee W. H., Elledge S. J. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. doi: 10.1101/gad.7.4.555. [DOI] [PubMed] [Google Scholar]
  10. Ferrell J. E., Jr, Martin G. S. Thrombin stimulates the activities of multiple previously unidentified protein kinases in platelets. J Biol Chem. 1989 Dec 5;264(34):20723–20729. [PubMed] [Google Scholar]
  11. Hunter T., Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994 Nov 18;79(4):573–582. doi: 10.1016/0092-8674(94)90543-6. [DOI] [PubMed] [Google Scholar]
  12. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  13. Kawakami A., Tian Q., Duan X., Streuli M., Schlossman S. F., Anderson P. Identification and functional characterization of a TIA-1-related nucleolysin. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8681–8685. doi: 10.1073/pnas.89.18.8681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kim M. Y., Linardic C., Obeid L., Hannun Y. Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation. J Biol Chem. 1991 Jan 5;266(1):484–489. [PubMed] [Google Scholar]
  16. Kojima H., Shinohara N., Hanaoka S., Someya-Shirota Y., Takagaki Y., Ohno H., Saito T., Katayama T., Yagita H., Okumura K. Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes. Immunity. 1994 Aug;1(5):357–364. doi: 10.1016/1074-7613(94)90066-3. [DOI] [PubMed] [Google Scholar]
  17. Kägi D., Ledermann B., Bürki K., Seiler P., Odermatt B., Olsen K. J., Podack E. R., Zinkernagel R. M., Hengartner H. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994 May 5;369(6475):31–37. doi: 10.1038/369031a0. [DOI] [PubMed] [Google Scholar]
  18. Kägi D., Vignaux F., Ledermann B., Bürki K., Depraetere V., Nagata S., Hengartner H., Golstein P. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528–530. doi: 10.1126/science.7518614. [DOI] [PubMed] [Google Scholar]
  19. Lipman M. L., Stevens A. C., Strom T. B. Heightened intragraft CTL gene expression in acutely rejecting renal allografts. J Immunol. 1994 May 15;152(10):5120–5127. [PubMed] [Google Scholar]
  20. Lowin B., Hahne M., Mattmann C., Tschopp J. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature. 1994 Aug 25;370(6491):650–652. doi: 10.1038/370650a0. [DOI] [PubMed] [Google Scholar]
  21. Luo J. H., Smith C. C., Kulka M., Aurelian L. A truncated protein kinase domain of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) expressed in Escherichia coli. J Biol Chem. 1991 Nov 5;266(31):20976–20983. [PubMed] [Google Scholar]
  22. Mathias S., Dressler K. A., Kolesnick R. N. Characterization of a ceramide-activated protein kinase: stimulation by tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10009–10013. doi: 10.1073/pnas.88.22.10009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mathias S., Younes A., Kan C. C., Orlow I., Joseph C., Kolesnick R. N. Activation of the sphingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1 beta. Science. 1993 Jan 22;259(5094):519–522. doi: 10.1126/science.8424175. [DOI] [PubMed] [Google Scholar]
  24. McLauchlan J., Clements J. B. DNA sequence homology between two co-linear loci on the HSV genome which have different transforming abilities. EMBO J. 1983;2(11):1953–1961. doi: 10.1002/j.1460-2075.1983.tb01684.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meikrantz W., Gisselbrecht S., Tam S. W., Schlegel R. Activation of cyclin A-dependent protein kinases during apoptosis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3754–3758. doi: 10.1073/pnas.91.9.3754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miyawaki T., Uehara T., Nibu R., Tsuji T., Yachie A., Yonehara S., Taniguchi N. Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol. 1992 Dec 1;149(11):3753–3758. [PubMed] [Google Scholar]
  27. Oltvai Z. N., Milliman C. L., Korsmeyer S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609–619. doi: 10.1016/0092-8674(93)90509-o. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Prescott D. M. The cell cycle and the control of cellular reproduction. Adv Genet. 1976;18:99–177. doi: 10.1016/s0065-2660(08)60438-1. [DOI] [PubMed] [Google Scholar]
  30. Raines M. A., Kolesnick R. N., Golde D. W. Sphingomyelinase and ceramide activate mitogen-activated protein kinase in myeloid HL-60 cells. J Biol Chem. 1993 Jul 15;268(20):14572–14575. [PubMed] [Google Scholar]
  31. Reed J. C. Bcl-2 and the regulation of programmed cell death. J Cell Biol. 1994 Jan;124(1-2):1–6. doi: 10.1083/jcb.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Russell G. J., Nagler-Anderson C., Anderson P., Bhan A. K. Cytotoxic potential of intraepithelial lymphocytes (IELs). Presence of TIA-1, the cytolytic granule-associated protein, in human IELs in normal and diseased intestine. Am J Pathol. 1993 Aug;143(2):350–354. [PMC free article] [PubMed] [Google Scholar]
  34. Sale G. E., Anderson P., Browne M., Myerson D. Evidence of cytotoxic T-cell destruction of epidermal cells in human graft-vs-host disease. Immunohistology with monoclonal antibody TIA-1. Arch Pathol Lab Med. 1992 Jun;116(6):622–625. [PubMed] [Google Scholar]
  35. Schwartzman R. A., Cidlowski J. A. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev. 1993 Apr;14(2):133–151. doi: 10.1210/edrv-14-2-133. [DOI] [PubMed] [Google Scholar]
  36. Shi L., Nishioka W. K., Th'ng J., Bradbury E. M., Litchfield D. W., Greenberg A. H. Premature p34cdc2 activation required for apoptosis. Science. 1994 Feb 25;263(5150):1143–1145. doi: 10.1126/science.8108732. [DOI] [PubMed] [Google Scholar]
  37. Smith C. C., Kulka M., Wymer J. P., Chung T. D., Aurelian L. Expression of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is required for virus growth and neoplastic transformation. J Gen Virol. 1992 Jun;73(Pt 6):1417–1428. doi: 10.1099/0022-1317-73-6-1417. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Taupin J. L., Tian Q., Kedersha N., Robertson M., Anderson P. The RNA-binding protein TIAR is translocated from the nucleus to the cytoplasm during Fas-mediated apoptotic cell death. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1629–1633. doi: 10.1073/pnas.92.5.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Taylor S. S., Knighton D. R., Zheng J., Ten Eyck L. F., Sowadski J. M. Structural framework for the protein kinase family. Annu Rev Cell Biol. 1992;8:429–462. doi: 10.1146/annurev.cb.08.110192.002241. [DOI] [PubMed] [Google Scholar]
  41. Tenner-Racz K., Racz P., Thomé C., Meyer C. G., Anderson P. J., Schlossman S. F., Letvin N. L. Cytotoxic effector cell granules recognized by the monoclonal antibody TIA-1 are present in CD8+ lymphocytes in lymph nodes of human immunodeficiency virus-1-infected patients. Am J Pathol. 1993 Jun;142(6):1750–1758. [PMC free article] [PubMed] [Google Scholar]
  42. Tian Q., Streuli M., Saito H., Schlossman S. F., Anderson P. A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell. 1991 Nov 1;67(3):629–639. doi: 10.1016/0092-8674(91)90536-8. [DOI] [PubMed] [Google Scholar]
  43. Veis D. J., Sorenson C. M., Shutter J. R., Korsmeyer S. J. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 1993 Oct 22;75(2):229–240. doi: 10.1016/0092-8674(93)80065-m. [DOI] [PubMed] [Google Scholar]
  44. Vivier E., Rochet N., Kochan J. P., Presky D. H., Schlossman S. F., Anderson P. Structural similarity between Fc receptors and T cell receptors. Expression of the gamma-subunit of Fc epsilon RI in human T cells, natural killer cells and thymocytes. J Immunol. 1991 Dec 15;147(12):4263–4270. [PubMed] [Google Scholar]
  45. Wang L., Miura M., Bergeron L., Zhu H., Yuan J. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 1994 Sep 9;78(5):739–750. doi: 10.1016/s0092-8674(94)90422-7. [DOI] [PubMed] [Google Scholar]
  46. Wang R., Murphy K. M., Loh D. Y., Weaver C., Russell J. H. Differential activation of antigen-stimulated suicide and cytokine production pathways in CD4+ T cells is regulated by the antigen-presenting cell. J Immunol. 1993 May 1;150(9):3832–3842. [PubMed] [Google Scholar]
  47. Wu J. Y., Zhou Z. Y., Judd A., Cartwright C. A., Robinson W. S. The hepatitis B virus-encoded transcriptional trans-activator hbx appears to be a novel protein serine/threonine kinase. Cell. 1990 Nov 16;63(4):687–695. doi: 10.1016/0092-8674(90)90135-2. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES