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eIF2α kinases provide a new solution to the puzzle of substrate specificity

Nature Structural & Molecular Biology volume 12, pages 835–838 (2005)Cite this article

The stress-activated protein kinases PKR and GCN2 regulate protein synthesis by phosphorylating the α subunit of translation initiation factor 2. Three recent studies reveal the molecular basis for the exquisite substrate specificity of this family of kinases and address the role of interlobe flexibility in kinase activation.

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Figure 1: Activation of PKR and its effect on cell processes.

References

  1. Hinnebusch, A.G. Mechanism and regulation of initiator methionyl-tRNA binding to ribosomes-in Translational Control of Gene Expression (eds. Sonenberg, N., Hershey, J.W.B. & Mathews, M.B.) 185–243 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, USA, 2000).

    Google Scholar 

  2. Lu, P.D., Harding, H.P. & Ron, D. J. Cell Biol. 167, 27–33 (2004).

    Article  CAS  Google Scholar 

  3. Vattem, K.M. & Wek, R.C. Proc. Natl. Acad. Sci. USA 101, 11269–11274 (2004).

    Article  CAS  Google Scholar 

  4. Proud, C.G. Semin. Cell Dev. Biol. 16, 3–12 (2005).

    Article  CAS  Google Scholar 

  5. Dar, A.C., Dever, T.E. & Sicheri, F. Cell 122, 887–900 (2005).

    Article  CAS  Google Scholar 

  6. Dey, M. et al. Cell 122, 901–913 (2005).

    Article  CAS  Google Scholar 

  7. Padyana, A.K., Qiu, H., Roll-Mecak, A., Hinnebusch, A.G. & Burley, S.K. J. Biol. Chem. 280, 29289–29299 (2005).

    Article  CAS  Google Scholar 

  8. Kostura, M. & Mathews, M.B. Mol. Cell. Biol. 9, 1576–1586 (1989).

    Article  CAS  Google Scholar 

  9. Zhang, F. et al. J. Biol. Chem. 276, 24946–24958 (2001).

    Article  CAS  Google Scholar 

  10. Ung, T.L., Cao, C., Lu, J., Ozato, K. & Dever, T.E. EMBO J. 20, 3728–3737 (2001).

    Article  CAS  Google Scholar 

  11. Hubbard, S.R. Nat. Rev. Mol. Cell Biol. 5, 464–471 (2004).

    Article  CAS  Google Scholar 

  12. Romano, P.R. et al. Mol. Cell. Biol. 18, 2282–2297 (1998).

    Article  CAS  Google Scholar 

  13. Mellor, H. & Proud, C.G. Biochem. Biophys. Res. Commun. 178, 430–437 (1991).

    Article  CAS  Google Scholar 

  14. Dar, A.C. & Sicheri, F. Mol. Cell 10, 295–305 (2002).

    Article  CAS  Google Scholar 

  15. Kawagishi-Kobayashi, M., Silverman, J.B., Ung, T.K. & Dever, T.E. Mol. Cell. Biol. 17, 4146–4158 (1997).

    Article  CAS  Google Scholar 

  16. Dey, M. et al. Mol. Cell. Biol. 25, 3063–3075 (2005).

    Article  CAS  Google Scholar 

  17. Dhaliwal, S. & Hoffman, D.W. J. Mol. Biol. 334, 187–195 (2003).

    Article  CAS  Google Scholar 

  18. Nonato, M.C., Widom, J. & Clardy, J. J. Biol. Chem. 277, 17057–17061 (2002).

    Article  CAS  Google Scholar 

  19. Ito, T., Marintchev, A. & Wagner, G. Structure (Camb). 12, 1693–1704 (2004).

    Article  CAS  Google Scholar 

  20. Qiu, H., Garcia-Barrio, M.T. & Hinnebusch, A.G. Mol. Cell. Biol. 18, 2697–2711 (1998).

    Article  CAS  Google Scholar 

  21. Wek, S.A., Zhu, S. & Wek, R.C. Mol. Cell. Biol. 15, 4497–4506 (1995).

    Article  CAS  Google Scholar 

  22. Qiu, H., Dong, J., Hu, C., Francklyn, C.S. & Hinnebusch, A.G. EMBO J. 20, 1425–1438 (2001).

    Article  CAS  Google Scholar 

  23. Qiu, H., Hu, C., Dong, J. & Hinnebusch, A.G. Genes Dev. 16, 1271–1280 (2002).

    Article  CAS  Google Scholar 

  24. Johnson, L., Lowe, E., Noble, M. & Owen, D. FEBS Lett. 430, 1–11 (1998).

    Article  CAS  Google Scholar 

  25. Huse, M. & Kuriyan, J. Cell 109, 275–282 (2002).

    Article  CAS  Google Scholar 

  26. Nolen, B., Taylor, S. & Ghosh, G. Mol. Cell 15, 661–675 (2004).

    Article  CAS  Google Scholar 

Download references

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  1. Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, US National Institutes of Health, Bethesda, 20892, Maryland, USA

    Alan G Hinnebusch

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Hinnebusch, A. eIF2α kinases provide a new solution to the puzzle of substrate specificity. Nat Struct Mol Biol 12, 835–838 (2005). https://doi.org/10.1038/nsmb1005-835

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