Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs

Cellular function is based on protein-protein interactions. A large proportion of these interactions involves the binding of short linear motifs (SLiMs) by folded globular domains. These interactions are regulated by post-translational modifications, such as phosphorylation, that create and break motif binding sites or tune the affinity of the interactions. In addition, motif-based interactions are involved in targeting serine/threonine kinases and phosphatases to their substrate and contribute to the specificity of the enzymatic actions regulating which sites are phosphorylated. Here, we review how SLiM-based interactions assist in determining the specificity of serine/threonine kinases and phosphatases, and how phosphorylation, in turn, affects motif-based interactions. We provide examples of SLiM-based interactions that are turned on/off, or are tuned by serine/threonine phosphorylation and exemplify how this affects SLiM-based protein complex formation.

Automated summary

Cellular function relies on protein-protein interactions, which often involve the binding of short linear motifs by folded globular domains. These interactions are regulated by post-translational modifications like phosphorylation, which can alter motif binding sites or modulate interaction affinity. Understanding how these interactions work is crucial in determining the specificity and function of enzymes like serine/threonine kinases and phosphatases.