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Protein phosphorylation is one of the most abundant posttranslational modifications affecting cellular function in both lower and higher life forms. 1 Reversible protein phosphorylation is an essential mechanism for regulating basic functions such as DNA replication, cell cycle control, gene transcription, protein translation, and energy metabolism. Such control is achieved by protein kinases and protein phosphatases. All protein kinases catalyze the transfer of the γ-phosphate group of ATP to the hydroxyl groups of serine, threonine, or tyrosine residues in protein substrates, with the exception of histidine kinases (which phosphorylate histidine residues). The significance of protein phosphorylation in eukaryotic signaling pathways is illustrated by the fact that protein kinase domains are found in about 2% of eukaryotic proteins including those of yeast, flies and humans. 2 Moreover, approximately 30% of cellular proteins contain covalently bound phosphate, and abnormal levels of protein phosphorylation are a cause or consequence of major diseases such as cancer, diabetes, and rheumatoid arthritis. 1 For example, the first discovered proto-oncogene v-Src encodes an aberrantly regulated tyrosine kinase. 3 Phosphorylation not only activates or deactivates a protein target, but can also alter the rate at which a protein is degraded, its ability to translocate from one subcellular compartment to another, and its capacity to bind with other proteins. Therefore, it is the spatial and temporal