Kinases transfer the γ-phosphate of ATP to other biological molecules, serving as chemical messengers that make the tight regulation of cell-signaling pathways possible. For example, non-receptor tyrosine kinases are found in the cytoplasm (not membrane-bound) and transfer the γ-phosphate of ATP to tyrosine residues of other proteins, often turning these proteins “on” or “off” in the context of their respective signaling pathway. This notion of “on” or “off” can be useful to holistically conceptualize these pathways but is a gross oversimplification; in reality, many of these enzymes are multi-domain proteins that can exist in multiple conformational states, participate in multiple protein-protein interactions, and experience a gradient of variable activity levels depending on these states. The molecular mechanisms that govern the activity of these kinases is extraordinarily complex, and though much has been discovered in recent years, much remains to be understood, especially for the Tec family of non-receptor tyrosine kinases.
The active conformation of kinases is highly conserved across almost all non-metabolic, Eukaryotic Protein Kinases. Furthermore, the equilibrium of inactive to active conformers differs between kinase domains, resulting in some kinase domains having higher activity levels than others. Numerous kinase catalytic domain structures have been solved in both their catalytically active and inactive conformers. The active conformation of kinases is highly conserved across almost all non-metabolic Eukaryotic Protein Kinases. Furthermore, the equilibrium of inactive to active conformers differs between kinases, resulting in some kinases having higher activity levels than others. Some kinases are intrinsically in the active conformation, whereas others require additional events (e.g. post-translation modification or interactions with other domains or proteins) to drive them into the active form.