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:

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

Oncogene volume 22, pages 4524–4530 (2003)Cite this article

Abstract

Disabled-2 (Dab2; also known as p96 and DOC-2) is a signal transduction protein that has been implicated in the control of cell growth. Dab2 is known to be a phosphoprotein, but little is known about the kinases that phosphorylate Dab2. We have found that Dab2 phosphorylation is markedly increased during the mitosis phase of the cell cycle. This phosphorylation is blocked by roscovitine, a selective inhibitor of cyclin-dependent kinases. Dab2 robustly coimmunoprecipitates from cells with the cyclin-dependent kinase cdc2, and purified cdc2 can phosphorylate purified Dab2 fusion proteins in vitro on multiple sites. Cellular phosphorylation of Dab2 by cdc2 promotes the association of Dab2 with Pin1, a peptidylprolyl isomerase that regulates the rate of Dab2 dephosphorylation. These findings reveal that Dab2 is differentially phosphorylated during the cell cycle by cdc2 and provide a potential feedback mechanism by which Dab2 inhibition of cell growth and proliferation may be regulated.

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

Similar content being viewed by others

References

  • Ajiro K, Yoda K, Utsumi K and Nishikawa Y . (1996). J. Biol. Chem., 271, 13197–13201.

  • Albertsen HM, Smith SA, Melis R, Williams B, Holik P, Stevens J and White R . (1996). Genomics, 33, 207–213.

  • Endicott JA, Noble ME and Tucker JA . (1999). Curr. Opin. Struct. Biol., 9, 738–744.

  • Fazili Z, Sun W, Mittelstaedt S, Cohen C and Xu XX . (1999). Oncogene, 18, 3104–3113.

  • Ferrell Jr JE . (2002). Curr. Opin. Cell. Biol., 14, 140–148.

  • Fulop V, Colitti CV, Genest D, Berkowitz RS, Yiu GK, Ng SW, Szepesi J and Mok SC . (1998). Oncogene, 17, 419–424.

  • Gertler FB, Bennett RL, Clark MJ and Hoffmann FM . (1989). Cell, 58, 103–113.

  • Haystead TA, Sim AT, Carling D, Honnor RC, Tsukitani Y, Cohen P and Hardie DG . (1989). Nature, 337, 78–81.

  • He J, Lau AG, Yaffe MB and Hall RA . (2001a). J. Biol. Chem., 276, 41559–41565.

  • He J, Smith ER and Xu XX . (2001b). J. Biol. Chem., 276, 26814–26818.

  • Hocevar BA, Smine A, Xu XX and Howe PH . (2001). EMBO J., 20, 2789–2801.

  • Holmes JK and Solomon MJ . (1996). J. Biol. Chem., 271, 25240–25246.

  • Howell BW, Gertler FB and Cooper JA . (1997a). EMBO J., 16, 121–132.

  • Howell BW, Hawkes R, Soriano P and Cooper JA . (1997b). Nature, 389, 733–737.

  • Inoue A, Sato O, Homma K and Ikebe M . (2002). Biochem. Biophys. Res. Commun., 292, 300–307.

  • Keshvara L, Benhayon D, Magdaleno S and Curran T . (2001). J. Biol. Chem., 276, 16008–16014.

  • Keshvara L, Magdaleno S, Benhayon D and Curran T . (2002). J. Neurosci., 22, 4869–4877.

  • Kishimoto T and Okumura E . (1997). Prog. Cell Cycle Res., 3, 241–249.

  • Kwon YG, Lee SY, Choi Y, Greengard P and Nairn AC . (1997). Proc. Natl. Acad. Sci. USA, 94, 2168–2173.

  • Lu KP, Liou YC and Zhou XZ . (2002). Trends Cell. Biol., 12, 164–172.

  • Mok SC, Chan WY, Wong KK, Cheung KK, Lau CC, Ng SW, Baldini A, Colitti CV, Rock CO and Berkowitz RS . (1998). Oncogene, 16, 2381–2387.

  • Mok SC, Wong KK, Chan RK, Lau CC, Tsao SW, Knapp RC and Berkowitz RS . (1994). Gynecol. Oncol., 52, 247–252.

  • Morris SM, Arden SD, Roberts RC, Kendrick-Jones J, Cooper JA, Luzio JP and Buss F . (2002). Traffic, 3, 331–341.

  • Morris SM and Cooper JA . (2001). Traffic, 2, 111–123.

  • Sheldon M, Rice DS, D'Arcangelo G, Yoneshima H, Nakajima K, Mikoshiba K, Howell BW, Cooper JA, Goldowitz D and Curran T . (1997). Nature, 389, 730–733.

  • Sheng Z, Sun W, Smith E, Cohen C and Xu XX . (2000). Oncogene, 19, 4847–4854.

  • Smith ER, Capo-chichi CD, He J, Smedberg JL, Yang DH, Prowse AH, Godwin AK, Hamilton TC and Xu XX . (2001). J. Biol. Chem., 276, 47303–47310.

  • Suganuma M, Fujiki H, Furuya-Suguri H, Yoshizawa S, Yasumoto S, Kato Y, Fusetani N and Sugimura T . (1990). Cancer Res., 50, 3521–3525.

  • Tseng CP, Ely BD, Pong RC, Wang Z, Zhou J and Hsieh JT . (1999). J. Biol. Chem., 274, 31981–31986.

  • Veeranna, Shetty KT, Link WT, Jaffe H, Wang J and Pant HC . (1995). J. Neurochem., 64, 2681–2690.

  • Verdecia MA, Bowman ME, Lu KP, Hunter T and Noel JP . (2000). Nat. Struct. Biol., 7, 639–643.

  • Wang SC, Makino K, Xia W, Kim JS, Im SA, Peng H, Mok SC, Singletary SE and Hung MC . (2001). Oncogene, 20, 6960–6964.

  • Wang Z, Tseng CP, Pong RC, Chen H, McConnell JD, Navone N and Hsieh JT . (2002). J. Biol. Chem., 277, 12622–12631.

  • Ware ML, Fox JW, Gonzalez JL, Davis NM, Lambert de Rouvroit C, Russo CJ, Chua Jr SC, Goffinet AM and Walsh CA . (1997). Neuron, 19, 239–249.

  • Xu XX, Yang W, Jackowski S and Rock CO . (1995). J. Biol. Chem., 270, 14184–14191.

  • Xu XX, Yi T, Tang B and Lambeth JD . (1998). Oncogene, 16, 1561–1569.

  • Zhou J and Hsieh JT . (2001). J. Biol. Chem., 276, 27793–27798.

  • Zieve GW, Turnbull D, Mullins JM and McIntosh JR . (1980). Exp. Cell. Res., 126, 397–405.

Download references

Acknowledgements

We thank Michael Yaffe for kindly supplying the construct for expressing GST-Pin1 and Amanda Castleberry and Anthony Lau for excellent technical assistance. This work was supported by National Institutes of Health grants RO1-HL-64713 (to RA Hall), RO1-CA-79716 (to XX Xu) and RO1-CA-75389 (to XX Xu) and also by a Distinguished Young Investigator in Medical Research award from the WM Keck Foundation to RAH.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, Atlanta, 30322, GA, USA

    Junqi He, Jianguo Xu & Randy A Hall

  2. Medical Science Division, Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, 19111, PA, USA

    Xiang-Xi Xu

Authors
  1. Junqi He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianguo Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang-Xi Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Randy A Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Randy A Hall.

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, J., Xu, J., Xu, XX. et al. Cell cycle-dependent phosphorylation of Disabled-2 by cdc2. Oncogene 22, 4524–4530 (2003). https://doi.org/10.1038/sj.onc.1206767

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206767

Keywords

This article is cited by

Search

Advanced search

Quick links