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FEBS J. 2013 Jan;280(2):324-45. doi: 10.1111/j.1742-4658.2012.08609.x. Epub 2012 May 21.

Protein Ser/Thr phosphatases--the ugly ducklings of cell signalling.

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  • 1Department of Microbiology, Immunology and Cancer Biology, Center for Cell Signaling, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA.


This review traces the historical origins and conceptual developments leading to the current state of knowledge of the three superfamilies of protein Ser/Thr phosphatases. 'PR enzyme' was identified as an enzyme that inactivates glycogen phosphorylase, although it took 10 years before this ugly duckling was recognized for its true identity as a protein Ser/Thr phosphatase. Ethanol denaturation for purification in the 1970s yielded a phosphatase that exhibited broad specificity, which was resolved into type-1 and type-2 phosphatases in the 1980s. More recent developments show that regulation and specificity are achieved through assembly of multisubunit holoenzymes, transient phosphorylation and the action of inhibitor proteins. Still not widely appreciated, there are hundreds of discrete protein Ser/Thr phosphatases available to counteract protein kinases, offering potential therapeutic targets. Signalling networks and modelling schemes need to incorporate the full gamut of protein Ser/Thr phosphatases and their interconnections.

© 2012 The Author Journal compilation © 2012 FEBS.

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