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Updated: Jul 30, 2025

Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
Substrate and phosphorylation site selection by phosphoprotein phosphatases
Hieu Nguyen1, Arminja N Kettenbach2
1Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA.
Abstract:
Dynamic protein phosphorylation and dephosphorylation are essential regulatory mechanisms that ensure proper cellular signaling and biological functions. Deregulation of either reaction has been implicated in several human diseases. Here, we focus on the mechanisms that govern the specificity of the dephosphorylation reaction. Most cellular serine/threonine dephosphorylation is catalyzed by 13 highly conserved phosphoprotein phosphatase (PPP) catalytic subunits, which form hundreds of holoenzymes by binding to regulatory and scaffolding subunits. PPP holoenzymes recognize phosphorylation site consensus motifs and interact with short linear motifs (SLiMs) or structural elements distal to the phosphorylation site. We review recent advances in understanding the mechanisms of PPP site-specific dephosphorylation preference and substrate recruitment and highlight examples of their interplay in the regulation of cell division.
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