Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output.

ABSTRACT: Specificity within protein kinase signaling cascades is determined by direct and indirect interactions between kinases and their substrates. While the impact of localization and recruitment on kinase-substrate targeting can be readily assessed, evaluating the relative importance of direct phosphorylation site interactions remains challenging. In this study, we examine the STE20 family of protein serine-threonine kinases to investigate basic mechanisms of substrate targeting. We used peptide arrays to define the phosphorylation site specificity for the majority of STE20 kinases and categorized them into four distinct groups. Using structure-guided mutagenesis, we identified key specificity-determining residues within the kinase catalytic cleft, including an unappreciated role for the kinase

SUBMITTER: Miller CJ 

PROVIDER: S-EPMC6445471 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature