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A monkey wrench in the kinase machine

Last year Zhang, Kuriyan and colleagues demonstrated that an asymmetric dimer interaction between EGF receptor kinase domains is a key element of receptor activation. They now show that a cellular protein that inhibits receptor activity targets this dimer interface, not only uncovering an important regulatory mechanism but also opening a new route to therapeutic kinase inhibition.

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Figure 1: Schematic model of EGFR activation.
Figure 2: Schematic model of inhibition of the EGFR kinase by Mig6.

References

  1. Holbro, T. & Hynes, N.E. Annu. Rev. Pharmacol. Toxicol. 44, 195–217 (2004).

    Article  CAS  Google Scholar 

  2. Hynes, N.E. & Lane, H.A. Nat. Rev. Cancer 5, 341–354 (2005).

    Article  CAS  Google Scholar 

  3. Schlessinger, J. Science 300, 750–752 (2003).

    Article  CAS  Google Scholar 

  4. Ferby, I. et al. Nat. Med. 12, 568–573 (2006).

    Article  CAS  Google Scholar 

  5. Anastasi, S., Baietti, M.F., Frosi, Y., Alema, S. & Segatto, O. Oncogene published online, doi:10.1038/sj.onc.1210590 (18 June 2007).

    Google Scholar 

  6. Zhang, X. et al. Nature 450, 741–744 (2007).

    Article  CAS  Google Scholar 

  7. Zhang, X., Gureasko, J., Shen, K., Cole, P.A. & Kuriyan, J. Cell 125, 1137–1149 (2006).

    Article  CAS  Google Scholar 

  8. Schlessinger, J. Cell 103, 211–225 (2000).

    Article  CAS  Google Scholar 

  9. Blume-Jensen, P. & Hunter, T. Nature 411, 355–365 (2001).

    Article  CAS  Google Scholar 

  10. Heldin, C.H. Cell 80, 213–223 (1995).

    Article  CAS  Google Scholar 

  11. Ferguson, K.M. et al. Mol. Cell 11, 507–517 (2003).

    Article  CAS  Google Scholar 

  12. Burgess, A.W. et al. Mol. Cell 12, 541–552 (2003).

    Article  CAS  Google Scholar 

  13. Garrett, T.P. et al. Cell 110, 763–773 (2002).

    Article  CAS  Google Scholar 

  14. Ogiso, H. et al. Cell 110, 775–787 (2002).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Levinson, N.M. et al. PLoS Biol. 4, e144 (2006).

    Article  Google Scholar 

  17. Jeffrey, P.D. et al. Nature 376, 313–320 (1995).

    Article  CAS  Google Scholar 

  18. Ballotti, R. et al. EMBO J. 8, 3303–3309 (1989).

    Article  CAS  Google Scholar 

  19. Lammers, R., Van Obberghen, E., Ballotti, R., Schlessinger, J. & Ullrich, A. J. Biol. Chem. 265, 16886–16890 (1990).

    CAS  PubMed  Google Scholar 

  20. Hackel, P.O., Gishizky, M. & Ullrich, A. Biol. Chem. 382, 1649–1662 (2001).

    Article  CAS  Google Scholar 

  21. Anastasi, S. et al. Oncogene 22, 4221–4234 (2003).

    Article  CAS  Google Scholar 

  22. Lei, M., Robinson, M.A. & Harrison, S.C. Structure 13, 769–778 (2005).

    Article  CAS  Google Scholar 

  23. Depetris, R.S. et al. Mol. Cell 20, 325–333 (2005).

    Article  CAS  Google Scholar 

  24. Johnston, J.B. et al. Curr. Med. Chem. 13, 3483–3492 (2006).

    Article  CAS  Google Scholar 

Download references

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Leahy, D. A monkey wrench in the kinase machine. Nat Struct Mol Biol 14, 1120–1121 (2007). https://doi.org/10.1038/nsmb1207-1120

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