An atlas of the catalytically active liver and spleen kinases in chicken identified by chemoproteomics

Abstract

AbstractChicken is the first agricultural animal to have a sequenced genome, but current kinase annotations of Gallus gallus are overwhelmingly limited to the predictions generated based on homology or isolated studies focused on specific kinases. Our approach used chemical probes consisting of ATP and ADP derivatives binding to specific lysine residues within the ATP-binding pocket of kinases. Collectively, we identified 188 chicken kinases and corresponding 267 peptides labeled with the ATP and ADP acyl derivatives in chicken spleen and liver. The kinases identified here are publicly available through the database, Chickspress genome browser (http://geneatlas.arl.arizona.edu/cgi-bin/GeneAtlas/chickspress_genes.cgii). Analysis of putative functions of these chicken kinases indicates that kinases identified in this study might regulate hematological system development, necrosis, apoptosis, epithelial neoplasm, and other processes. The identified tissue-specific expression atlas of active chicken kinases along with the ATP binding sites of kinases provide the basis for the development of specific drug targets for multiple chicken diseases as well as starting point for inhibitor selectivity studies in this agriculturally important species. Moreover, this study will support future studies focused on identifying the role of these kinases in chicken growth, metabolism, and disease.