What is the significance of protein kinases in cellular signaling?

Protein kinases have crucial roles in cellular signaling, such as regulating cell growth and proliferation, gene expression, cell survival, metabolism, signal transduction and cell cycle progression. Protein kinases are involved in signal transduction, as kinases use ATP as a phosphate source to add phosphate groups to other proteins. This inactivates these proteins, and triggers a phosphorylation cascade. Phosphorylated proteins cause the amplification of a signal to generate a cellular response. These pathways regulate the activity of downstream effectors, causing changes in cellular mechanisms. Protein kinases are also involved in gene expression. Kinases phosphorylate transcription factors which can either activate or inhibit their activity. This then leads to changes in gene expression. In cell cycle progression, cyclin-dependent kinases (CDK) regulate different stages of the cell cycle by phosphorylating specific substrates. These substrates include other kinases, proteins, and transcription factors. Errors involving CDK activity may lead to uncontrolled cell division and the development of malignancies. Kinases also play a role in cell survival and apoptosis. For example, the PI3K/AKT/mTOR pathway is activated by growth factors and regulates cell survival. This is done by phosphorylating different substrates involved in cell cycle regulation and apoptosis.