Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The relative role of ErbB1–4 receptor tyrosine kinases in radiation signal transduction responses of human carcinoma cells

Oncogene volume 20, pages 1388–1397 (2001)Cite this article

An Erratum to this article was published on 05 July 2001

Abstract

Activation of the epidermal growth receptor (ErbB1) occurs within minutes of a radiation exposure. Immediate downstream consequences of this activation are currently indistinguishable from those obtained with growth factors (GF), e.g. stimulation of the pro-proliferative mitogen-activated protein kinase (MAPK). To identify potential differences, the effects of GFs and radiation on other members of the ErbB family have been compared in mammary carcinoma cell lines differing in their ErbB expression profiles. Treatment of cells with EGF (ErbB1-specific) or heregulin (ErbB4-specific) resulted in a hierarchic transactivations of ErbB2 and ErbB3 dependent on GF binding specificity. In contrast, radiation indiscriminately activated all ErbB species with the activation profile reflecting that cell's ErbB expression profile. Downstream consequences of these ErbB interactions were examined with MAPK after specifically inhibiting ErbB1 (or 4) with tyrphostin AG1478 or ErbB2 with tyrphostin AG825. MAPK activation by GFs or radiation was completely inhibited by AG1478 indicating total dependance on ErbB1 (or 4) depending on which ErbB is expressed. Inhibiting ErbB2 caused an enhanced MAPK response simulating an amplified ErbB1 (or 4) response. Thus ErbB2 is a modulator of ErbB1 (or 4) function leading to different MAPK response profiles to GF or radiation exposure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 4
Figure 5
Figure 3
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Abbott D, Holt JG . 1999 J. Biol. Chem. 274: 2732–2742

  • Akimoto T, Hunter NR, Buchmiller L, Mason K, Ang K, Milas L . 1999 Clin. Cancer Res. 5: 2884–2890

  • Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, Di Fiore PP, Kraus M . 1995 Oncogene 10: 1813–1821

  • Alimandi M, Wang LM, Bottaro D, Lee CC, Kuo A, Frankel M, Fedi P, Tang C, Lippman M, Pierce JH . 1997 EMBO J. 16: 5608–5617

  • Aubert JS, Dessolin S, Belmonte N, Li M, McKenzie FR, Staccini L, Villageois P, Barhanin B, Vernallis A, Smith AG, Ailhaud G, Dani C . 1999 J. Biol. Chem. 274: 24965–24972

  • Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG . 1997 J. Biol. Chem. 272: 217–221

  • Beier F, Taylor AC, LuValle P . 1999 J. Biol. Chem. 274: 30273–30279

  • Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH, Parson SJ . 1999 J. Biol. Chem. 274: 8335–8343

  • Brondello JM, McKensie FR, Sun H, Tonks NK, Poyssequr J . 1995 Oncogene 10: 1895–1904

  • Chen BK, Kung HC, Tsai TY, Chang WC . 2000 Mol. Pharmacol. 57: 153–161

  • Contessa JN, Reardon DB, Todd D, Dent P, Mikkelsen RB, Valerie K, Bowers GD, Schmidt-Ullrich RK . 1999 Clin. Cancer. Res. 5: 405–411

  • Dent P, Reardon DB, Park JS, Bowers GD, Logsodon C, Valerie K, Schmidt-Ullrich RK . 1999 Mol. Biol. Cell. 10: 2493–2506

  • Denu JM, Tanner KG . 1998 Biochemistry 37: 5633–5642

  • Earp HS, Dawson TL, Li X, Yu H . 1995 Breast Cancer Res. Treat. 35: 115–132

  • Fowles LF, Martin ML, Nelson L, Stacey KJ, Redd D, Clark YM, Nagamine Y, McMahon M, Hume DA, Ostrowski MC . 1998 Mol. Cell. Biol. 18: 5148–5156

  • Frederick L, Wan XY, Eley G, James CD . 2000 Cancer Res. 60: 1383–1387

  • Fry DW, Kraker AJ, McMichael A, Ambroso LA, Nelson JM, Leopold WR, Connors RW, Bridges R . 1994 Science 265: 1093–1095

  • Gamett DC, Greene T, Wagreich AR, Kim HH, Koland JG, Cerione RA . 1995 Biol. Chem. 270: 19022–19027

  • Gamett DC, Pearson G, Cerione RA, Friedberg I . 1997 J. Biol. Chem. 272: 12052–12056

  • Gotoh M, Toyoda M, Shibuya M . 1997 Mol. Cell. Biol. 17: 1824–1831

  • Graus-Porta D, Beerli RR, Daly JM, Hynes NE . 1997 EMBO J. 16: 1647–1655

  • Gulliford TJ, Huang GC, Ouyang X, Epstein RJ . 1997 Oncogene 15: 2219–2223

  • Huang GC, Ouyang X, Epstein RJ . 1998 Biochem. J. 331: 113–119

  • Kern FG, McLeskey SW, Khang L . 1994 Breast Cancer Res. Treat. 31: 153–165

  • Levitzki A, Gazit A . 1995 Science 267: 1782–1788

  • Li N, Schlessinger J, Margolis B . 1994 Oncogene 9: 3457–3465

  • O'Rourke DM, Kao GD, Singh N, Park BW, Muschel RJ, Wu CJ, Greene MI . 1998 Proc. Natl. Acad. Sci. U.S.A. 95: 10842–10847

  • Park JS, Carter S, Reardon DB, Schmidt-Ullrich RK, Dent P, Fisher PB . 1999 Mol. Cell. Biol. 10: 4231–4246

  • Park JS, Boyer S, Mitchell K, Gilfor D, Birrer M, Darlington G, El-Deiry W, Firestone GL, Munger K, Band V, Fisher PB, Dent P . 2000 J. Biol. Chem. 275: 18–28

  • Plowman GD, Culouscou JM, Whitney GS, Green JM, Carlton GW, Foy L, Neubauer MG, Shoyab M . 1993 Proc. Natl. Acad. Sci. USA 90: 1746–1750

  • Qian W, LeVea CM, Freeman JK, Dougall WC, Greene MI . 1994 Proc. Natl. Acad. Sci. USA 91: 1500–1504

  • Reardon DB, Contessa JN, Mikkelsen RB, Valerie K, Amir C, Dent P, Schmidt-Ullrich RK . 1999 Oncogene 18: 4756–4766

  • Redemann N, Holzmann B, Reuden TV, Wagner EF, Schlessinger J, Ullrich A . 1992 Mol. Cell. Biol. 12: 491–498

  • Riese DJ, Stern DF . 1998 Bioessays 20: 41–48

  • Sasaoka T, Langlois WJ, Bai F, Rose DW, Leitner JW, Decker SJ, Saltiel A, Gill GN, Kobayayashi M, Drasnin B, Olefsky JM . 1996 J. Biol. Chem. 271: 8338–8344

  • Schmidt-Ullrich R, Valerie K, Fogleman PB, Walters J . 1996 Radiation Res. 145: 81–85

  • Schmidt-Ullrich R, Contessa JN, Dent P, Mikkelsen RB, Valerie K, Reardon DB, Bowers G, Lin PS . 1999 Radiat. Oncol. Invest. 7: 321–330

  • Schmidt-Ullrich R, Dent P, Grant S, Mikkelsen RB, Valerie K . 2000 Radiat. Res. 153: 245–257

  • Schmidt-Ullrich R, Mikkelsen RB, Dent P, Todd D, Valerie K, Kavanagh B, Contessa J, Rorrer K, Chen P . 1997 Oncogene 15: 1191–1197

  • Sears R, DeGregori LG, Nevins JR . 1993 Mol. Cell. Biol. 3: 169–179

  • Todd DG, Mikkelsen RB, Rorrer WK, Valerie K, Schmidt-Ullrich RK . 1999 J. Rec. Signal Trans. Res. 19: 885–908

  • Tsai C, Levitzki A, Wu LH, Chang KT, Cheng CC, Gazit A, Perng RP . 1996 Cancer Res. 56: 1068–1074

  • Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z, Kolesnick RN . 1996 Nature 380: 75–79

  • Wang Y, Prywes R . 2000 Oncogene 19: 1379–1385

Download references

Acknowledgements

Supported by USPHS grants PO1 CA 72955 and RO1 CA 65896 (RK Schmidt-Ullrich), and the Mildred Scheel Deutsche Krebshilfe (G Lammering).

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA23298-0058, Virginia, USA

    G Bowers, D Reardon, T Hewitt, P Dent, R B Mikkelsen, K Valerie, G Lammering, C Amir & R K Schmidt-Ullrich

  2. Department of Neurosurgery, Emory University, Atlanta, Georgia, USA

    G Bowers

  3. Department of Basic Pharmaceutical Sciences, The University of Louisiana, Monroe, Louisiana, USA

    D Reardon

  4. Department of Radiation Oncology, Heinrich-Heine University, Duesseldorf, Germany

    G Lammering

Authors
  1. G Bowers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Reardon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Hewitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Dent
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R B Mikkelsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Valerie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G Lammering
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Amir
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R K Schmidt-Ullrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowers, G., Reardon, D., Hewitt, T. et al. The relative role of ErbB1–4 receptor tyrosine kinases in radiation signal transduction responses of human carcinoma cells. Oncogene 20, 1388–1397 (2001). https://doi.org/10.1038/sj.onc.1204255

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204255

Keywords

This article is cited by

Search

Advanced search

Quick links