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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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Protein Ser/Thr phosphatases--the ugly ducklings of cell signalling

David L Brautigan1

  • 1Department of Microbiology, Immunology and Cancer Biology, Center for Cell Signaling, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA. db8g@virginia.edu

The FEBS Journal
|April 24, 2012
PubMed

Insights

Protein Ser/Thr phosphatases, initially termed

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Signaling

Background:

  • Protein Ser/Thr phosphatases are crucial enzymes that counteract protein kinases.
  • Their historical identification and characterization have evolved significantly over decades.
  • Early research identified 'PR enzyme' which later became recognized as a protein Ser/Thr phosphatase.

Purpose of the Study:

  • To review the historical origins and conceptual evolution of protein Ser/Thr phosphatases.
  • To highlight the current understanding of their regulation and specificity.
  • To emphasize their therapeutic potential and importance in cellular signaling networks.

Main Methods:

  • Historical literature review.
  • Analysis of conceptual developments in phosphatase research.
  • Synthesis of current knowledge on enzyme regulation and specificity.

Main Results:

  • Protein Ser/Thr phosphatases were initially identified as 'PR enzyme' and later resolved into type-1 and type-2 phosphatases.
  • Modern understanding reveals regulation and specificity are achieved via multisubunit holoenzymes, phosphorylation, and inhibitors.
  • Hundreds of distinct protein Ser/Thr phosphatases exist, offering numerous therapeutic targets.

Conclusions:

  • The field has progressed from a single enzyme to recognizing a vast array of protein Ser/Thr phosphatases.
  • These phosphatases play critical roles in cellular signaling and represent significant therapeutic opportunities.
  • Future research and modeling must integrate the full spectrum of these enzymes and their complex interconnections.

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