BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

PI(3,4,5)P3 regulates the interaction between Akt and B23 in the nucleus

  • Kwon, Il-Sun (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Lee, Kyung-Hoon (Department of Anatomy, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Choi, Joung-Woo (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Ahn, Jee-Yin (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine)
  • Published : 2010.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Phosphatidylinositol (3,4,5)-triphosphate ($PIP_3$) is a lipid second messenger that employs a wide range of downstream effector proteins for the regulation of cellular processes, including cell survival, polarization and proliferation. One of the most well characterized cytoplasmic targets of $PIP_3$, serine/threonine protein kinase B (PKB)/Akt, promotes cell survival by directly interacting with nucleophosmin (NPM)/B23, the nuclear target of $PIP_3$. Here, we report that nuclear $PIP_3$ competes with Akt to preferentially bind B23 in the nucleoplasm. Mutation of Arg23 and Arg25 in the PH domain of Akt prevents binding to $PIP_3$, but does not disrupt the Akt/B23 interaction. However, treatment with phosphatases PTEN or SHIP abrogates the association between Akt and B23, indicating that nuclear $PIP_3$ regulates the Akt/B23 interaction by controlling the concentration and subcellular dynamics of these two proteins.

Keywords

References

  1. Maehama, T., Taylor, G. S. and Dixon, J. E. (2001) PTEN and myotubularin: novel phosphoinositide phosphatases. Annu. Rev. Biochem. 70, 247-279 https://doi.org/10.1146/annurev.biochem.70.1.247
  2. Krystal, G. (2000) Lipid phosphatases in the immune system. Semin. Immunol. 12, 397-403 https://doi.org/10.1006/smim.2000.0222
  3. Brunet, A., Datta, S. R. and Greenberg, M. E. (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr. Opin. Neurobiol. 11, 297-305 https://doi.org/10.1016/S0959-4388(00)00211-7
  4. Ahmed, N. N., Franke, T. F., Bellacosa, A., Datta, K., Gonzalez-Portal, M. E., Taguchi, T., Testa, J. R. and Tsichlis, P. N. (1993) The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential. Oncogene 8, 1957-1963
  5. Neri, L. M., Milani, D., Bertolaso, L., Stroscio, M., Bertagnolo, V. and Capitani, S. (1994) Nuclear translocation of phosphatidylinositol 3-kinase in rat pheochromocytoma PC 12 cells after treatment with nerve growth factor. Cell. Mol. Biol. (Noisy-le-grand) 40, 619-626
  6. Xuan Nguyen, T. L., Choi, J. W., Lee, S. B., Ye, K., Woo, S. D., Lee, K. H. and Ahn, J. Y. (2006) Akt phosphorylation is essential for nuclear translocation and retention in NGF-stimulated PC12 cells. Biochem. Biophys. Res. Commun. 349, 789-798 https://doi.org/10.1016/j.bbrc.2006.08.120
  7. Ahn, J. Y., Rong, R., Liu, X. and Ye, K. (2004) PIKE/nuclear PI 3-kinase signaling mediates the anti-apoptotic actions of NGF in the nucleus. Embo J. 23, 3995-4006 https://doi.org/10.1038/sj.emboj.7600392
  8. Bacqueville, D., Deleris, P., Mendre, C., Pieraggi, M. T., Chap, H., Guillon, G., Perret, B. and Breton-Douillon, M. (2001) Characterization of a G protein-activated phosphoinositide 3-kinase in vascular smooth muscle cell nuclei. J. Biol. Chem. 276, 22170-22176 https://doi.org/10.1074/jbc.M011572200
  9. Cocco, L., Maraldi, N. M., Capitani, S., Martelli, A. M. and Manzoli, F. A. (2001) Nuclear localization and signalling activity of inositol lipids. Ital. J. Anat. Embryol. 106, 31-43
  10. Ye, K. and Ahn, J. Y. (2008) Nuclear phosphoinositide signaling. Front Biosci. 13, 540-548 https://doi.org/10.2741/2699
  11. Ahn, J. Y., Liu, X., Cheng, D., Peng, J., Chan, P. K., Wade, P. A. and Ye, K. (2005) Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the anti-apoptotic actions of NGF by inhibiting CAD. Mol. Cell 18, 435-445 https://doi.org/10.1016/j.molcel.2005.04.010
  12. Lee, S. B., Xuan Nguyen, T. L., Choi, J. W., Lee, K. H., Cho, S. W., Liu, Z., Ye, K., Bae, S. S. and Ahn, J. Y. (2008) Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival. Proc. Natl. Acad. Sci. U.S.A. 105, 16584-16589 https://doi.org/10.1073/pnas.0807668105
  13. Choi, J. W., Lee, S. B., Ahn, J. Y. and Lee, K. H. (2008) Disruption of ATP binding destabilizes NPM/B23 and inhibits anti-apoptotic function. BMB Rep. 41, 840-845 https://doi.org/10.5483/BMBRep.2008.41.12.840
  14. Choi, J. W., Lee, S. B., Kim, C. K., Lee, K. H., Cho, S. W. and Ahn, J. Y. (2008) Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23 stability. FEBS Lett. 582, 1073-1080 https://doi.org/10.1016/j.febslet.2008.02.059
  15. Liu, X., Liu, Z., Jang, S. W., Ma, Z., Shinmura, K., Kang, S., Dong, S., Chen, J., Fukasawa, K. and Ye, K. (2007) Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival. Proc. Natl. Acad. Sci. U.S.A. 104, 9679-9684 https://doi.org/10.1073/pnas.0701806104
  16. Neri, L. M., Martelli, A. M., Borgatti, P., Colamussi, M. L., Marchisio, M. and Capitani, S. (1999) Increase in nuclear phosphatidylinositol 3-kinase activity and phosphatidylinositol (3, 4, 5) trisphosphate synthesis precede PKC-zeta translocation to the nucleus of NGF-treated PC12 cells. Faseb J. 13, 2299-2310
  17. Tanaka, K., Horiguchi, K., Yoshida, T., Takeda, M., Fujisawa, H., Takeuchi, K., Umeda, M., Kato, S., Ihara, S., Nagata, S. and Fukui, Y. (1999) Evidence that a phosphatidylinositol 3,4,5-trisphosphate-binding protein can function in nucleus. J. Biol. Chem. 274, 3919-3922 https://doi.org/10.1074/jbc.274.7.3919
  18. James, S. R., Downes, C. P., Gigg, R., Grove, S. J., Holmes, A. B. and Alessi, D. R. (1996) Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem. J. 315, 709-713 https://doi.org/10.1042/bj3150709
  19. Frech, M., Andjelkovic, M., Ingley, E., Reddy, K. K., Falck, J. R. and Hemmings, B. A. (1997) High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272, 8474- 8481 https://doi.org/10.1074/jbc.272.13.8474
  20. Wu, H., Goel, V. and Haluska, F. G. (2003) PTEN signaling pathways in melanoma. Oncogene 22, 3113-3122 https://doi.org/10.1038/sj.onc.1206451
  21. Sly, L. M., Rauh, M. J., Kalesnikoff, J., Buchse, T. and Krystal, G. (2003) SHIP, SHIP2, and PTEN activities are regulated in vivo by modulation of their protein levels: SHIP is up-regulated in macrophages and mast cells by lipopolysaccharide. Exp. Hematol. 31, 1170-1181 https://doi.org/10.1016/j.exphem.2003.09.011
  22. Deleris, P., Bacqueville, D., Gayral, S., Carrez, L., Salles, J. P., Perret, B. and Breton-Douillon, M. (2003) SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles. J. Biol. Chem. 278, 38884-38891 https://doi.org/10.1074/jbc.M300816200
  23. Yamada, K. M. and Araki, M. (2001) Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J. Cell. Sci. 114, 2375-2382
  24. Ahn, J. Y., Liu, X., Liu, Z., Pereira, L., Cheng, D., Peng, J., Wade, P. A., Hamburger, A. W. and Ye, K. (2006) Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase. Embo J. 25, 2083-2095 https://doi.org/10.1038/sj.emboj.7601111
  25. Hu, Y., Yao, J., Liu, Z., Liu, X., Fu, H. and Ye, K. (2005) Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation. Embo J. 24, 3543-3554 https://doi.org/10.1038/sj.emboj.7600823
  26. Nicholson, K. M. and Anderson, N. G. (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14, 381-395 https://doi.org/10.1016/S0898-6568(01)00271-6

Cited by

  1. Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas vol.106, pp.6, 2015, https://doi.org/10.1111/cas.12669
  2. Nuclear Akt promotes neurite outgrowth in the early stage of neuritogenesis vol.45, pp.9, 2012, https://doi.org/10.5483/BMBRep.2012.45.9.114
  3. Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion vol.32, pp.3, 2015, https://doi.org/10.1016/j.devcel.2014.12.019
  4. Insights into the regulation of neuronal viability by nucleophosmin/B23 vol.240, pp.6, 2015, https://doi.org/10.1177/1535370215579168
  5. Molecular alterations in AKT and its protein activation in human lung carcinomas vol.43, pp.12, 2012, https://doi.org/10.1016/j.humpath.2012.03.015
  6. Role of T cell–nuclear factor κB in transplantation vol.26, pp.3, 2012, https://doi.org/10.1016/j.trre.2011.07.005
  7. Nuclear phosphoinositides and their roles in cell biology and disease vol.46, pp.5, 2011, https://doi.org/10.3109/10409238.2011.609530
  8. Modulation of Ciliary Phosphoinositide Content Regulates Trafficking and Sonic Hedgehog Signaling Output vol.34, pp.3, 2015, https://doi.org/10.1016/j.devcel.2015.06.016
  9. Phospholipase C-η2 is required for retinoic acid-stimulated neurite growth vol.124, pp.5, 2013, https://doi.org/10.1111/jnc.12122
  10. Nuclear Lipids in the Nervous System: What they do in Health and Disease vol.42, pp.2, 2017, https://doi.org/10.1007/s11064-016-2085-8
  11. Phospholipase C-η2 interacts with nuclear and cytoplasmic LIMK-1 during retinoic acid-stimulated neurite growth vol.145, pp.2, 2016, https://doi.org/10.1007/s00418-015-1390-7
  12. Structure and catalytic mechanism of human protein tyrosine phosphatome vol.45, pp.12, 2012, https://doi.org/10.5483/BMBRep.2012.45.12.240
  13. Neuroprotection Signaling of Nuclear Akt in Neuronal Cells vol.23, pp.3, 2014, https://doi.org/10.5607/en.2014.23.3.200