Abstract
IL-2 deprivation triggers apoptosis in the murine T cell line TS1αβ, a process that can be blocked by overexpression of Bcl-2. Here we show that Bcl-2 and Ras proteins interact in mitochondria from TS1αβ cells in the presence or absence of IL-2, as evidenced by co-immunoprecipitation. All three Ras proteins, K-, N- and H-Ras, interact with Bcl-2; however, their mitochondrial localization is differentially regulated in IL-2-supplemented or -deprived cells. K-Ras is found in mitochondria only in IL-2-supplemented cells, whereas H-Ras is observed in mitochondria only after IL-2 withdrawal. N-Ras is detected in mitochondria under both experimental conditions. Bcl-2 transfection partially restored K- and N-Ras association with mitochondria in IL-2-deprived cells and rendered H-Ras association independent of IL-2 withdrawal. Inhibitors of Ras posttranslational processing did not alter the IL-2-induced differential pattern of mitochondrial localization. The processed forms of K- and N-Ras associated with mitochondria, although unprocessed H-Ras was also detected in mitochondria from mevastatin-treated cells. These results evidence a distinct behavior among the three Ras proteins in TS1αβ cells, depending on IL-2 supply, and suggest homologue-specific roles for Ras proteins in IL-2-dependent events.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Broome HE, Dargan CM, Bressent EF, Krajewski S and Reed JC. . 1995a Immunology 84: 375–381.
Broome HE, Dargan CM, Krajewski S and Reed JC. . 1995b J. Immunol. 155: 2311–2317.
Casey PJ. . 1995 Science 268: 221–225.
Chen C and Faller DV. . 1996 J. Biol. Chem. 271: 2376–2379.
De Jong D, Prons FA, Mason DY, Reed JC, Van Ommen GB and Kevin PM. . 1994 Cancer Res. 54: 256–260.
Deng G and Podack P. . 1993 Proc. Natl. Acad. Sci. USA 90: 2189–2196.
Downward JD. . 1998 Curr. Opin. Genet. Dev. 8: 49–54.
Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM and Weinberg RA. . 1993 Nature 363: 45–51.
Fan J and Bertino JR. . 1997 Oncogene 14: 2595–2607.
Fernandez-Sarabia MJ and Bischoff JR. . 1993 Nature 366: 274–275.
Glomset JA and Farnsworth CC. . 1994 Annu. Rev. Cell Biol. 10: 181–205.
Gómez J, Martínez-AC, Fernández B, García A and Rebollo A. . 1996 J. Immunol. 157: 2772–2781.
Gómez J, Martínez-AC, Fernández B, García A and Rebollo A. . 1997 Eur. J. Immunol. 27: 1610–1618.
Gómez J, Martínez-AC, González A, García A and Rebollo A. . 1998 Oncogene 16: In press.
Hall A. . 1998 Science 279: 509–514.
Hatakeyama M, Tsudo M, Minamoto S, Kono T, Doi T, Miyata M, Miyasaka M and Taniguchi T. . 1989 Science 244: 551–556.
Hsu YT, Wolter KG and Youle RJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 3668–3672.
Izquierdo M, Reif K and Cantrell D. . 1995 Immunol. Today 16: 159–164.
James GL, Goldstein JL and Brown MS. . 1995 J. Biol. Chem. 270: 6221–6226.
James GL, Goldstein JL, Brown MS, Rawson TE, Somers TC, McDowell RS, Crowley CW, Lucas BK, Levinson AD and Marsters JC. . 1993 Science 260: 1937–1942.
James GL, Goldstein JL, Pathak RK, Anderson RGW and Brown MS. . 1994 J. Biol. Chem. 269: 14182–14190.
Jones MJ and Jackson JH. . 1998 J. Biol. Chem. 273: 1782–1787.
Kato K, Cox AD, Hisaka MM, Graham SM, Buss JE and Der CJ. . 1992 Proc. Natl. Acad. Sci. USA 89: 6403–6407.
Krajewski S, Tanaka S, Takayama S, Schibler MJ, Frentosn W and Reed JC. . 1993 Cancer Res. 53: 47017–47024.
Lerner EC, Zhang TT, Knowles DB, Quian Y, Hamilton AD and Sebti SM. . 1997 Oncogene 15: 1283–1288.
Miyazaki T, Liu ZJ, Kawahara A, Minami Y, Yamada K, Tsujimoto Y, Barsoumian L, Pelmutter RM and Taniguchi T. . 1995 Cell 81: 223–231.
Okada T, Masuda T, Shinkai M, Kariya K and Kataoka T. . 1996 J. Biol. Chem. 271: 4671–4678.
Pérez-Sala D and Mollinedo F. . 1994 Biochem. Biophys. Res. Commun. 199: 1209–1215.
Pitton C, Rebollo A, Van Snick J, Theze J and Garcia A. . 1993 Cytokine 5: 362–371.
Reis Y, Stradley SJ, Gierasch LM, Brown MS and Goldstein JL. . 1991 Proc. Natl. Acad. Sci. USA 88: 732–736.
Ridley AJ. . 1995 Curr. Opin. Genet. Dev. 5: 24–30.
Shibasaki F, Kondo E, Akagi T and McKeon F. . 1997 Nature 386: 728–731.
Siddqui AA, Garland JR, Dalton MB and Sinensky M. . 1998 J. Biol. Chem. 273: 3712–3717.
Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M and Sugamura K. . 1992 Science 275: 379–382.
Thissen JA, Gross JM, Subramanian K, Meyer T and Casey PJ. . 1997 J. Biol. Chem. 272: 30362–30370.
Wang HG, Miyashita T, Takayama S, Sato T, Torigoe T, Krajewski S, Tanaka S, Hovey L, Troppmair J, Rapp U and Reed J. . 1994 Oncogene 9: 2751–2756.
Wang HG, Rapp UR and Reed JC. . 1996 Cell 87: 629–638.
Weller M, Malipiero U, Aguzzi A, Reed JC and RFontana A. . 1995 J. Clin. Invest. 85: 2633–2639.
Whyte DB, Kirschmeier P, Hockenberry TN, Nuñez-Oliva I, James L, Catino JJ, Bishop WB and Pai JK. . 1997 J. Biol. Chem. 272: 14459–14464.
Wyllie AH. . 1995 Curr. Opin. Genet. Dev. 5: 97–104.
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP and Wang X. . 1997 Science 275: 1129–1132.
Zamzami N, Brenner C, Marzo I, Susin SA and Kroemer G. . 1998 Oncogene 16: 2265–2282.
Zhang FL, Kirschmeier P, Carr D, James L, Bond RW, Wang L, Patton R, Windsor W, Syto R, Zhang R and Bishop WR. . 1997 J. Biol. Chem. 272: 10232–10239.
Acknowledgements
We thank Dr S Lamas for his support, and C Mark for editorial assistance. The Department of Immunology and Oncology was founded and is supported by the Spanish Research Council (CSIC) and Pharmacia & Upjohn.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rebollo, A., Pérez-Sala, D. & Martínez-A, C. Bcl-2 differentially targets K-, N-, and H-Ras to mitochondria in IL-2 supplemented or deprived cells: Implications in prevention of apoptosis. Oncogene 18, 4930–4939 (1999). https://doi.org/10.1038/sj.onc.1202875
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202875