Protein kinases are a crucial component of signaling pathways involved in a wide range of cellular responses, including growth, proliferation, differentiation, and migration. Systematic investigation of protein kinases is critical to better understand phosphorylation-mediated signaling pathways and may provide insights into the development of potential therapeutic drug targets. Here we perform a systems-level analysis of the mouse kinome by analyzing multi-omics data. We used bulk and single-cell transcriptomic data from the C57BL/6J mouse strain to define tissue- and cell-type-specific expression of protein kinases, followed by investigating variations in sequence and expression between C57BL/6J and DBA/2J strains. We then profiled a deep brain phosphoproteome from C57BL/6J and DBA/2J strains as well as their reciprocal hybrids to infer the activity of the mouse kinome. Finally, we performed phenome-wide association analysis using the BXD recombinant inbred (RI) mice (a cross between C57BL/6J and DBA/2J strains) to identify any associations between variants in protein kinases and phenotypes. Collectively, our study provides a comprehensive analysis of the mouse kinome by investigating genetic sequence variation, tissue-specific expression patterns, and associations with downstream phenotypes.
Keywords: BXD mice; C57BL/6J; DBA/2J; PheWAS; kinase activity; kinome; mouse; omics; protein expression; protein kinase; proteome.
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