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Controlling Abl: auto-inhibition and co-inhibition?

Nature Cell Biology volume 6, pages 3–7 (2004)Cite this article

Abstract

Auto-inhibition describes the capacity of proteins to adopt a self-imposed latent conformation. Recently, a crystal structure of the Abl tyrosine kinase has revealed its ability to auto-inhibit. However, a separate body of work suggests that other cellular proteins also inhibit Abl. To reconcile the crystal structure with Abl inhibitors, I propose that Abl is controlled by cellular 'co-inhibitors' that bind Abl, stabilizing the auto-inhibited conformation. The implication of co-inhibition on Abl function is discussed.

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Figure 1: Summary of the primary and tertiary structures of Abl.
Figure 2: A model of co-inhibition and conformational transitions for Abl.

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Acknowledgements

I wish to thank J. Zhu at the La Jolla Scientific Management for the artwork. I owe this perspective to the many talented investigators who have worked on Abl in my lab and around the world. Many worthy citations are omitted from this article solely because of page limits. Our work on Abl has been supported by the National Institutes of Health (USA).

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  1. Division of Biological Sciences and the Cancer Center, Section of Molecular Biology, University of California, San Diego, La Jolla, 92093-0322, CA, USA

    Jean Y. J. Wang

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Wang, J. Controlling Abl: auto-inhibition and co-inhibition?. Nat Cell Biol 6, 3–7 (2004). https://doi.org/10.1038/ncb0104-3

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