Skip to main content
SpringerLink
Log in

Abi enhances Abl-mediated Cdc2 phosphorylation and inactivation

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Abelson tyrosine kinase (Abl) is a non-receptor tyrosine kinase which is frequently coupled with adaptor proteins to interact with its substrates for the regulation of cytoskeleton rearrangement, cell growth and apoptosis in response to a variety of biological stimuli. The Abl interactor (Abi) family members were first identified as adaptor proteins of Abl for regulating Abl transforming and kinase activity. In the present study, we used a yeast two-hybrid screen to identify Cdc2 as a novel Abi-binding protein. This finding led us to investigate the role of Abi in linking Abl and Cdc2. These three proteins formed a trimeric complex inDrosophila and mammalian cells. The expression of Abi in cells greatly enhanced the formation of the Abl-Cdc2 complex, suggesting that Abi functions as an adaptor protein facilitating the binding between Abl and Cdc2. We show that Abi promotes Abl-mediated phosphorylation of Cdc2 at tyrosine 15 and inactivation of Cdc2 kinase activity. Furthermore, coexpression of Abl and Abi inDrosophila S2 cells led to suppression of cell growth. These data suggest that Abl signaling may be involved in the downregulation of Cdc2 kinase in cell cycle control.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bedi A, Barber JP, Bedi GC, el-Deiry WS, Sidransky D, Vala MS, Akhtar AJ, Hilton J, Jones RJ. BCR-ABL-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: A mechanism of resistance to multiple anticancer agents. Blood 86:1148–1158;1995.

    PubMed  Google Scholar 

  2. Biesova Z, Piccoli C, Wong WT. Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth. Oncogene 14:233–241;1997.

    Article  PubMed  Google Scholar 

  3. Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Druker BJ, Lydon NB. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 56:100–104;1996.

    PubMed  Google Scholar 

  4. Dai Z, Pendergast A. Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity. Genes Dev 9:2569–2582;1995.

    PubMed  Google Scholar 

  5. Fan PD, Goff SP. Abl interactor 1 binds to sos and inhibits epidermal growth factor- and v-Abl-induced activation of extracellular signal-regulated kinases. Mol Cell Biol 20:7591–7601;2000.

    Article  PubMed  Google Scholar 

  6. Ferris DK, White GA, Kelvin DJ, Copeland TD, Li CC, Longo DL. p34cdc2 is physically associated with and phosphorylated by a cdc2-specific tyrosine kinase. Cell Growth Differ 2:343–349;1991.

    PubMed  Google Scholar 

  7. Flynn DC. Adaptor proteins. Oncogene 20:6270–6272;2001.

    Article  PubMed  Google Scholar 

  8. Gotoh A, Broxmeyer HE. The function of BCR/ABL and related proto-oncogenes. Curr Opin Hematol 4:3–11;1997.

    PubMed  Google Scholar 

  9. Ichigotani Y, Yokozaki S, Fukuda Y, Hamaguchi M, Matsuda S. Forced expression of NESH suppresses motility and metastatic dissemination of malignant cells. Cancer Res 62:2215–2219;2002.

    PubMed  Google Scholar 

  10. Ikeguchi A, Yang HY, Gao G, Goff SP. Inhibition of v-Abl transformation in 3T3 cells over-expressing different forms of the Abelson interactor protein Abi-1. Oncogene 20:4926–4934;2001.

    Article  PubMed  Google Scholar 

  11. Juang J-L, Hoffmann FM.Drosophila Abelson interacting protein (dAbi) is a positive regulator of Abelson tyrosine kinase activity. Oncogene 18:5138–5147;1999.

    Article  PubMed  Google Scholar 

  12. Kharbanda S, Ren R, Pandey P, Shafman TD, Feller SM, Weichselbaum RR, Kufe DW. Activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents. Nature 376:785–788;1995.

    Article  PubMed  Google Scholar 

  13. Kipreos ET, Wang JY. Differential phosphorylation of c-Abl in cell cycle determined by cdc2 kinase and phosphatase activity. Science 248:217–220;1990.

    PubMed  Google Scholar 

  14. Lee DF, Chen CC, Hsu TA, Juang JL. A baculovirus superinfection system: Efficient vehicle for gene transfer intoDrosophila S2 cells. J Virol 74:11873–11880;2000.

    Article  PubMed  Google Scholar 

  15. Miyazaki K, Matsuda S, Ichigotani Y, Takenouchi Y, Hayashi K, Fukuda Y, Nimura Y, Hamaguchi M. Isolation and characterization of a novel human gene (NESH) which encodes a putative signaling molecule similar to e3B1 protein. Biochim Biophys Acta 1493:237–241;2000.

    PubMed  Google Scholar 

  16. Morgan DO. Principles of CDK regulation. Nature 374:131–134;1995.

    Article  PubMed  Google Scholar 

  17. Nebreda AR, Gannon JV, Hunt T. Newly synthesized protein(s) must associate with p34cdc2 to activate MAP kinase and MPF during progesterone-induced maturation ofXenopus oocytes. Embo J 14:5597–5607;1995.

    PubMed  Google Scholar 

  18. Nishii K, Kabarowski JH, Gibbons DL, Griffiths SD, Titley I, Wiedemann LM, Greaves MF. ts BCR-ABL kinase activation confers increased resistance to genotoxic damage via cell cycle block. Oncogene 13:2225–2234;1996.

    PubMed  Google Scholar 

  19. Nurse P. Checkpoint pathways come of age. Cell 91:865–867;1997.

    Article  PubMed  Google Scholar 

  20. Ramet M, Pearson A, Manfruelli P, Li X, Koziel H, Gobel V, Chung E, Krieger M, Ezekowitz RA.Drosophila scavenger receptor CI is a pattern recognition receptor for bacteria. Immunity 15:1027–1038;2001.

    Article  PubMed  Google Scholar 

  21. Rogers SL, Wiedemann U, Stuurman N, Vale RD. Molecular requirements for actin-based lamella formation inDrosophila S2 cells. J Cell Biol 162:1079–1088;2003.

    Article  PubMed  Google Scholar 

  22. Schneider I. Cell lines derived from late embryonic stages ofDrosophila melanogaster. J Embryol Exp Morphol 27:353–365;1972.

    PubMed  Google Scholar 

  23. Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegard M, Betsholtz C, Di Fiore PP. EPS8 and E3B1 transduce signals from Ras to Rac. Nature 401:290–293;1999.

    Article  PubMed  Google Scholar 

  24. Shi Y, Alin K, Goff S. Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. Genes Dev 9:2583–2597;1995.

    PubMed  Google Scholar 

  25. Slupianek A, Hoser G, Majsterek I, Bronisz A, Malecki M, Blasiak J, Fishel R, Skorski T. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G2/M phase, and protection from apoptosis. Mol Cell Biol 22:4189–4201;2002.

    Article  PubMed  Google Scholar 

  26. Stiewe T, Parssanedjad K, Esche H, Opalka B, Putzer BM. E1A overcomes the apoptosis block in BCR-ABL+ leukemia cells and renders cells susceptible to induction of apoptosis by chemotherapeutic agents. Cancer Res 60:3957–3964;2000.

    PubMed  Google Scholar 

  27. Stradal T, Courtney KD, Rottner K, Hahne P, Small JV, Pendergast AM. The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia. Curr Biol 11:891–895;2001.

    Article  PubMed  Google Scholar 

  28. Tani K, Sato S, Sukezane T, Kojima H, Hirose H, Hanafusa H, Shishido T. Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase. J Biol Chem 278:21685–21692;2003.

    Article  PubMed  Google Scholar 

  29. Van Etten RA. Cycling, stressed-out and nervous: Cellular functions of c-Abl. Trends Cell Biol 9:179–86;1999.

    Article  PubMed  Google Scholar 

  30. Wang B, Mysliwiec T, Krainc D, Jensen RA, Sonoda G, Testa JR, Golemis EA, Kruh GD. Identification of ArgBP1, an Arg protein tyrosine kinase binding protein that is the human homologue of a CNS-specificXenopus gene. Oncogene 12:1921–1929;1996.

    PubMed  Google Scholar 

  31. Zou X, Calame K. Signaling pathways activated by oncogenic forms of Abl tyrosine kinase. J Biol Chem 274:18141–18144;1999.

    Article  PubMed  Google Scholar 

  32. Zukerberg LR, Patrick GN, Nikolic M, Humbert S, Wu CL, Lanier LM, Gertler FB, Vidal M, Van Etten RA, Tsai LH. Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth. Neuron 26:633–646;2000.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan

    Tzu-Yang Lin, Chiu-Hui Huang & Wen-Gang Chou

  2. Division of Molecular and Genomic Medicine, National Health Research Institutes, 128 Yen-Chiu-Yuan Road, Sec. 2, 115, Taipei, Taiwan

    Chiu-Hui Huang & Jyh-Lyh Juang

Authors
  1. Tzu-Yang Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiu-Hui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen-Gang Chou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jyh-Lyh Juang
    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

Lin, TY., Huang, CH., Chou, WG. et al. Abi enhances Abl-mediated Cdc2 phosphorylation and inactivation. J Biomed Sci 11, 902–910 (2004). https://doi.org/10.1007/BF02254375

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02254375

Key Words

Search

Navigation