Protein phosphorylation is a key event in signal transduction pathways. When upstream signals are stimulated,
protein kinases are activated and phosphorylate their substrates, modulating their localization, conformation, and activity.
In some cases, phosphorylated substrates become recognizable to other proteins—such interactions transduce and propel
the signal onward. Certain domains specifically recognize phosphorylated residues of proteins, regulating cell growth and
differentiation. Because the proteins that contain these domains also mediate diseases that are caused by dysregulated signal
transduction, small molecules that inhibit such motifs are attractive candidates for the treatment of diseases, such as
cancer. In this review, we summarize the domains that recognize phosphorylated proteins, particularly serine- and
threonine-phosphorylated sequences in target proteins. In addition, we introduce a high-throughput screen that we developed
to identify small-molecule inhibitors of phosphorylation-dependent protein-protein interactions. An example is presented,
and the potential uses of this system are discussed.
Keywords: Protein phosphorylation, protein-protein interaction, small molecule, high throughput screening, Plk1, polo box
domain, purpurogallin, Protein phosphorylation, protein-protein interaction, small molecule, high throughput screening, Plk1, polo box domain, purpurogallin, Cancer Therapy, Molecular Targets, small-molecule inhibitors
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