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.

  • Original Paper
  • Published:

Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

Oncogene volume 21, pages 5823–5834 (2002)Cite this article

Abstract

Shc family of docking proteins, ShcA, ShcB and ShcC, play roles in cellular signal transduction by binding to phosphotyrosine residues of various activated receptor tyrosine kinases. Both ShcB and ShcC proteins are selectively expressed in the neural system of adult mouse tissues. In most of neuroblastoma cells, obvious tyrosine phosphorylation of ShcC was observed, whereas expression of ShcB was considerably low. Phosphoproteins associated with hyperphosphorylated ShcC were purified from neuroblastoma cell lines, and identified by mass-spectrometry. Anaplastic lymphoma kinase (ALK), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the PTB domain of ShcC in three neuroblastoma cells. In vitro kinase assay revealed that ShcC is a potent substrate of the activated ALK kinase. The ALK gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the ALK kinase, which results in hyperphosphorylation of ShcC. Constitutive activation of ALK appeared to interfere with signals from other receptor tyrosine kinases. ALK-ShcC signal activation, possibly caused by co-amplification with the N-myc gene, might give additional effects on malignant tumor progression of neuroblastoma.

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 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Akiyama K, Kanda N, Yamada M, Tadokoro K, Matsunaga T, Nishi Y . 1994 Nucleic Acids Res. 22: 187–193

  • Andrechek ER, Hardy WR, Siegel PM, Rudnicki MA, Cardiff RD, Muller WJ . 2000 Proc. Natl. Acad. Sci. USA 97: 3444–3449

  • Asai N, Murakami H, Iwashita T, Takahashi M . 1996 J. Biol. Chem. 271: 17644–17649

  • Bischof D, Pulford K, Mason DY, Morris SW . 1997 Mol. Cell. Biol. 17: 2312–2325

  • Blume-Jensen P, Hunter T . 2001 Nature 411: 355–365

  • Collins LR, Ricketts WA, Yeh L, Cheresh D . 1999 J. Cell Biol. 147: 1561–1568

  • Conti L, De Fraja C, Gulisano M, Migliaccio E, Govoni S, Cattaneo E . 1997 Proc. Natl. Acad. Sci. USA 94: 8185–8190

  • Conti L, Sipione S, Magrassi L, Bonfanti L, Rigamonti D, Pettirossi V, Peschanski M, Haddad B, Pelicci P, Milanesi G, Pelicci G, Cattaneo E . 2001 Nat. Neurosci. 4: 579–586

  • Dankort D, Maslikowski B, Warner N, Kanno N, Kim H, Wang Z, Moran MF, Oshima RG, Cardiff RD, Muller WJ . 2001 Mol. Cell. Biol. 21: 1540–1551

  • Fujimoto J, Shiota M, Iwahara T, Seki N, Satoh H, Mori S, Yamamoto T . 1996 Proc. Natl. Acad. Sci. USA 93: 4181–4186

  • George RE, Kenyon RM, McGuckin AG, Malcolm AJ, Pearson AD, Lunec J . 1996 Oncogene 12: 1583–1587

  • Goga A, McLaughlin J, Afar DE, Saffran DC, Witte ON . 1995 Cell 82: 981–988

  • Gotoh N, Tojo A, Shibuya M . 1996 EMBO J. 15: 6197–6204

  • Hiemstra JL, Schneider SS, Brodeur GM . 1994 Prog. Clin. Biol. Res. 385: 51–57

  • Ikeda I, Ishizaka Y, Tahira T, Suzuki T, Onda M, Sugimura T, Nagao M . 1990 Oncogene 5: 1291–1296

  • Ishikawa S . 1977 Acta. Pathol. Jpn. 27: 697–711

  • Ishikawa S, Ohshima Y, Suzuki T, Oboshi S . 1979 Acta. Patho. Jpn. 29: 289–301

  • Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T, Mori S, Ratzkin B, Yamamoto T . 1997 Oncogene 14: 439–449

  • Iwamatsu A . 1992 Electrophoresis 13: 142–147

  • Iwamatsu A, Yoshida-Kubomura N . 1996 J. Biochem. (Tokyo) 120: 29–34

  • Kohl NE, Legouy E, DePinho RA, Nisen PD, Smith RK, Gee CE, Alt FW . 1986 Nature 319: 73–77

  • Kuefer MU, Look AT, Pulford K, Behm FG, Pattengale PK, Mason DY, Morris SW . 1997 Blood 90: 2901–2910

  • Kuga N, Yoshida K, Seido T, Oboshi S, Koide T, Shimosato Y, Nomura T . 1975 Gann 66: 547–560

  • Lai KM, Pawson T . 2000 Genes Dev. 14: 1132–1145

  • Lamant L, Pulford K, Bischof D, Morris SW, Mason DY, Delsol G, Mariame B . 2000 Am. J. Pathol. 156: 1711–1721

  • Laminet AA, Apell G, Conroy L, Kavanaugh WM . 1996 J. Biol. Chem. 271: 264–269

  • Layfield LJ, Thompson JK, Dodge RK, Kerns BJ . 1995 J. Surg. Oncol. 59: 21–27

  • Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT . 1994 Science 263: 1281–1284

  • Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X, Witte DP . 1997 Oncogene 14: 2175–2188

  • Nakamura N, Chin H, Miyasaka N, Miura O . 1996a J. Biol. Chem. 271: 19483–19488

  • Nakamura T, Muraoka S, Sanokawa R, Mori N . 1998 J. Biol. Chem. 273: 6960–6967

  • Nakamura T, Sanokawa R, Sasaki Y, Ayusawa D, Oishi M, Mori N . 1996b Oncogene 13: 1111–1121

  • Nojiri H, Manya H, Isono H, Yamana H, Nojima S . 1999 FEBS Lett. 453: 140–144

  • O'Bryan JP, Martin CB, Songyang Z, Cantley LC, Der CJ . 1996a J. Biol. Chem. 271: 11787–11791

  • O'Bryan JP, Songyang Z, Cantley L, Der CJ, Pawson T . 1996b Proc. Natl. Acad. Sci. USA 93: 2729–2734

  • Ole NJ, Alexandre P, Matthias M . 1996 Rapid Commun. Mass Spectrom. 10: 1371–1378

  • Passoni L, Scardino A, Bertazzoli C, Gallo B, Coluccia AM, Lemonnier FA, Kosmatopoulos K, Gambacorti-Passerini C . 2002 Blood 99: 2100–2106

  • Pawson T, Gish GD, Nash P . 2001 Trends Cell Biol. 11: 504–511

  • Pelicci G, Dente L, De Giuseppe A, Verducci-Galletti B, Giuli S, Mele S, Vetriani C, Giorgio M, Pandolfi PP, Cesareni G, Pelicci PG . 1996 Oncogene 13: 633–641

  • Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Pawson T, Pelicci PG . 1992 Cell 70: 93–104

  • Pelicci G, Lanfrancone L, Salcini AE, Romano A, Mele S, Grazia Borrello M, Segatto O, Di Fiore PP, Pelicci PG . 1995 Oncogene 11: 899–907

  • Perucho M, Goldfarb M, Shimizu K, Lama C, Fogh J, Wigler M . 1981 Cell 27: 467–476

  • Rozakis-Adcock M, Fernley R, Wade J, Pawson T, Bowtell D . 1993 Nature 363: 83–85

  • Sakai R, Henderson JT, O'Bryan JP, Elia AJ, Saxton TM, Pawson T . 2000 Neuron 28: 819–833

  • Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Nishida J, Yazaki Y, Hirai H . 1994 J. Biol. Chem. 269: 32740–32746

  • Sakai R, Nakamoto T, Ozawa K, Aizawa S, Hirai H . 1997 Oncogene 14: 1419–1426

  • Southern EM . 1975 J. Mol. Biol. 94: 51–69

  • Stanton LW, Schwab M, Bishop JM . 1986 Proc. Natl. Acad. Sci. USA 83: 1772–1776

  • Stoica GE, Kuo A, Aigner A, Sunitha I, Souttou B, Malerczyk C, Caughey DJ, Wen D, Karavanov A, Riegel AT, Wellstein A . 2001 J. Biol. Chem. 276: 16772–16779

  • Sugimoto T, Tatsumi E, Takeda K, Minato K, Sagawa K, Minowada J . 1984 J. Natl. Cancer Inst. 72: 923–928

  • Tanabe K, Kiryu-Seo S, Nakamura T, Mori N, Tsujino H, Ochi T, Kiyama H . 1998 Brain Res. Mol. Brain Res. 53: 291–296

  • van der Geer P, Wiley S, Gish GD, Pawson T . 1996 Curr. Biol. 6: 1435–1444

  • van der Geer P, Wiley S, Lai VK, Olivier JP, Gish GD, Stephens R, Kaplan D, Shoelson S, Pawson T . 1995 Curr. Biol. 5: 404–412

  • Wimmer K, Zhu XX, Lamb BJ, Kuick R, Ambros PF, Kovar H, Thoraval D, Motyka S, Alberts JR, Hanash SM . 1999 Oncogene 18: 233–238

Download references

Acknowledgements

We thank Dr M Ohki for comments and technical advices, and Dr H Nakadate for tissue samples of the patients. Izumi Miyake and Yuko Hakomori are the recipients of Research Resident Fellowships from the Foundation for Promotion of Cancer Research, Japan.

Author information

Authors and Affiliations

  1. Cancer Signal Transduction Project, National Cancer Center Research Institute, 5-1-1 Tsukuji, Chuo-ku, 104-0045, Tokyo, Japan

    Izumi Miyake, Yuko Hakomori & Ryuichi Sakai

  2. Cancer Genomics Division, National Cancer Center Research Institute, 5-1-1 Tsukuji, Chuo-ku, 104-0045, Tokyo, Japan

    Toshie Gamou

  3. Central Laboratory for Key Technology, Kirin Brewery Co. Ltd., 1-13-5 Fukuura, Kanazawa-ku, Yokohama-shi, 236-0004, Kanagawa, Japan

    Azusa Shinohara & Akihiro Iwamatsu

  4. Department of Oncology & Pharmacodynamics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, 20-4-8588, Tokyo, Japan

    Masaki Saito

  5. Department of Pediatrics, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara-shi, 228-8555, Kanagawa, Japan

    Izumi Miyake

Authors
  1. Izumi Miyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuko Hakomori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Azusa Shinohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshie Gamou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masaki Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akihiro Iwamatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ryuichi Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryuichi Sakai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyake, I., Hakomori, Y., Shinohara, A. et al. Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines. Oncogene 21, 5823–5834 (2002). https://doi.org/10.1038/sj.onc.1205735

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205735

Keywords

This article is cited by

Search

Advanced search

Quick links