Proteomic Characterization of Human Kinases Across Tissue Types: Implications for Kinase Activated Drugs

Kinases catalyze the activation of certain nucleoside and nucleotide analogue drugs used in the treatment of various cancers and viral infections. As these drugs require intracellular phosphorylation to their active form, the abundance of kinases within tissues is a key factor in determining both variability in response and off target effects. In this study, we quantified and compared protein abundances of kinases in commercially available pooled S9 fractions of adult human liver (n=50), kidney (n=12), lung (n=5), intestine (n=4), and individual adult primary hepatocytes (n=8). These data were compared to the proteomic abundance profile of red blood cells (n=4), from healthy donors, and bone marrow samples (n=44) from acute myeloid leukemia patients, in addition to kinase abundance in human plasma from the publicly available database Protein Atlas. Kinase protein abundance was estimated using the total protein approach in pmol/mg total protein. We detected 364 kinases, including 23 drug metabolizing kinases, with varying abundances across tissue and biofluid types. Four drug metabolizing kinases, ADK, CMPK1, NME1, and NME3, were detected in all sample types. Additionally, by comparing tissue to plasma abundance ratios of kinases to known secreted versus non-secreted marker proteins, we showed that kinases are primarily present in plasma due to tissue shedding, with few (PGK1, PKM, AK1, NME1) that may be present as part of extracellular vesicles. Lastly, we identified the presence of 24 kinases commonly targeted by inhibitors across sample types. Overall, this study advances the understanding of the presence and variability of kinases in different tissues.