The intrinsic substrate specificity of the human tyrosine kinome. (https://pubmed.ncbi.nlm.nih.gov/38720073/)

These scientists wanted to understand how certain proteins in our bodies are changed in a specific way by other proteins called kinases. They focused on a type of protein kinase called tyrosine kinases, which play an important role in how our tissues grow and function. These tyrosine kinases can add a chemical group called phosphate to other proteins at specific spots called tyrosine residues.

To figure out how each tyrosine kinase chooses which proteins to modify, the scientists used a method called combinatorial peptide arrays. This allowed them to see the preferred patterns of amino acids around the tyrosine residue that each tyrosine kinase likes to target. They found that different tyrosine kinases have unique preferences for these patterns, which helps them identify which tyrosine kinase is likely to modify a specific protein.

By analyzing data from experiments where cells were stimulated with growth factors, treated with anti-cancer drugs, or exposed to cancer-causing mutations, the scientists were able to pinpoint which tyrosine kinases were behaving differently in these conditions. They also compared the preferences of tyrosine kinases with another type of protein called SH2 domains that bind to phosphorylated tyrosine residues, and found interesting connections between them.

Overall, the scientists discovered that the preferences of tyrosine kinases for specific protein sequences have remained similar across different species, suggesting that this interaction has been important throughout evolution. This study helps us understand how these proteins work in our bodies and how they might be involved in diseases like cancer.

Yaron-Barir TM., Joughin BA., Huntsman EM., Kerelsky A., Cizin DM., Cohen BM., Regev A., Song J., Vasan N., Lin TY., Orozco JM., Schoenherr C., Sagum C., Bedford MT., Wynn RM., Tso SC., Chuang DT., Li L., Li SS., Creixell P., Krismer K., Takegami M., Lee H., Zhang B., Lu J., Cossentino I., Landry SD., Uduman M., Blenis J., Elemento O., Frame MC., Hornbeck PV., Cantley LC., Turk BE., Yaffe MB., Johnson JL. The intrinsic substrate specificity of the human tyrosine kinome. Nature. 2024 May 8. doi: 10.1038/s41586-024-07407-y.