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Src autoinhibition: let us count the ways

Nature Structural Biology volume 6, pages 711–714 (1999)Cite this article

Abstract

Src family tyrosine kinases are key cellular signaling enzymes whose catalytic activities are tightly controlled. Recent structural and mutational studies have revealed additional intricacies in the autoinhibitory mechanisms by which catalytic activity is repressed.

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Figure 1: a, Domain organization of Src family tyrosine kinases.
Figure 2: Mispositioning of the C helix.
Figure 3: a, Close up view of the region of the activation loop containing Tyr 416.

References

  1. Superti-Furga, G. & Courtneidge, S.A. Bioessays 17, 321–330 ( 1993).

    Article  Google Scholar 

  2. Brown, M.T. & Cooper, J.A. Biochim. Biophys. Acta 1287, 121–149 (1996).

    Google Scholar 

  3. Xu, W., Harrison, S.C. & Eck, M.J. Nature 385, 595– 602 (1997).

    Article  CAS  Google Scholar 

  4. Williams, J.C. et al. J. Mol. Biol. 274, 757– 775 (1997).

    Article  CAS  Google Scholar 

  5. Sicheri, F., Moarefi, I. & Kuriyan, J. Nature 385, 602– 609 (1997).

    Article  CAS  Google Scholar 

  6. Xu, W., Doshi, A., Lei, M., Eck, M.J. & Harrison, S.C. Mol. Cell 3, 629– 638 (1999).

    Article  CAS  Google Scholar 

  7. Schindler, T. et al. Mol. Cell 3, 639–648 (1999).

    Article  CAS  Google Scholar 

  8. Gonfloni, S., Frischknecht, F., Way, M. & Superti-Furga, G. Nature Struct. Biol. 6, 760–764 (1999).

    Article  CAS  Google Scholar 

  9. Pawson, T. Nature 373, 573–580 ( 1995).

    Article  CAS  Google Scholar 

  10. Kuriyan, J. & Cowburn, D. Annu. Rev. Biophys. Biomol. Struct. 26, 259–288 ( 1997).

    Article  CAS  Google Scholar 

  11. Hunter, T. Cell 49, 1–4 ( 1987).

    Article  CAS  Google Scholar 

  12. Nada, S., Okada, M., MacAuley, A., Cooper, J.A. & Nagawa, H. Nature 351, 69– 72 (1991).

    Article  CAS  Google Scholar 

  13. Matsuda, M., Mayer, B.J., Fukui, Y. & Hanafusa, H. Science 248, 1537–1539 (1990).

    Article  CAS  Google Scholar 

  14. Superti-Furga, G., Fumagalli, S., Koegl, M., Courtneidge, S.A. & Draetta, G. EMBO J. 12, 2625– 2634 (1993).

    Article  CAS  Google Scholar 

  15. Feng, S., Chen, J.K., Yu, H., Simon, J.A. & Schreiber, S.L. Science 266, 1241– 1247 (1994).

    Article  CAS  Google Scholar 

  16. Taylor, S.S. & Radio-Andzelm, E. Structure 2, 245–355 (1994).

    Article  Google Scholar 

  17. Johnson, L.N, Noble, M.E. & Owen, D.J. Cell 85, 149–158 (1996).

    Article  CAS  Google Scholar 

  18. Hubbard, S.R., Mohammadi, M. & Schlessinger, J. J. Biol. Chem. 273, 11987– 11990 (1998).

    Article  CAS  Google Scholar 

  19. Russo, A.A., Jeffrey, P.D. & Pavletich, N.P. Nature Struct. Biol. 3, 696 –700 (1996).

    Article  CAS  Google Scholar 

  20. Yamaguchi, H. & Hendrickson, W.A. Nature 384, 484–489 (1996).

    Article  CAS  Google Scholar 

  21. Canagarajah, B.J., Khokhlatchev, A., Cobb, M.H. & Goldsmith, E.J. Cell 90, 859–869 ( 1997).

    Article  CAS  Google Scholar 

  22. Hubbard, S.R. EMBO J. 16, 5572–5581 ( 1997).

    Article  CAS  Google Scholar 

  23. Kmiecik, T.E. & Shalloway, D. Cell 49, 65–73 (1987).

    Article  CAS  Google Scholar 

  24. Piwnica-Worms, H., Saunders, K.B., Roberts, T.M., Smith, A.E. & Cheng, A.E. Cell 49, 75–82 (1987).

    Article  CAS  Google Scholar 

  25. De Bondt, H.L et al. Nature 363, 595–602 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Mori, S., Ronnstrand, L., Yokote, K., Engstrom, A., Courtneidge, S.A., Claesson-Welsh L. & Heldin, C.H. EMBO J. 12, 2257–2264 ( 1993).

    Article  CAS  Google Scholar 

  28. Alonso, G., Koegl, M., Mazurenko, N. & Courtneidge, S.A. J. Biol. Chem. 270, 9840–9848 ( 1995).

    Article  CAS  Google Scholar 

  29. Moarefi, I. et al. Nature 385, 650–653 (1997).

    Article  CAS  Google Scholar 

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Acknowledgements

I thank M. Eck for providing the Src coordinates, and J. Till for helping with figure preparation and for manuscript comments.

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  1. the Department of Pharmacology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, 10016, NY, USA

    Stevan R. Hubbard

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  1. Stevan R. Hubbard
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Hubbard, S. Src autoinhibition: let us count the ways. Nat Struct Mol Biol 6, 711–714 (1999). https://doi.org/10.1038/11468

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