Fine-tuning of substrate preferences of the Src-family kinase Lck revealed through a high-throughput specificity screen.

ABSTRACT: The specificity of tyrosine kinases is attributed predominantly to localization effects dictated by non-catalytic domains. We developed a method to profile the specificities of tyrosine kinases by combining bacterial surface-display of peptide libraries with next-generation sequencing. Using this, we showed that the tyrosine kinase ZAP-70, which is critical for T cell signaling, discriminates substrates through an electrostatic selection mechanism encoded within its catalytic domain (Shah et al., 2016). Here, we expand this high-throughput platform to analyze the intrinsic specificity of any tyrosine kinase domain against thousands of peptides derived from human tyrosine phosphorylation sites. Using this approach, we find a difference in the electrostatic recognition of substrates between

SUBMITTER: Shah NH 

PROVIDER: S-EPMC5889215 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature