Targets for Signal-transducing Protein Kinases

The transduction of signals from the external medium across the plasma membrane into the cell is a process that is essential to the functioning of multicellular organisms. There are several basic mechanisms of signal transduction, many of which involve protein phosphorylation. Protein phosphorylation is ideally suited for signal transduction, since protein kinases have an inbuilt mechanism for signal amplification, and protein phosphatases provide a means of reversing the signal when the stimulus is removed. The most common type of signal-transducing protein kinase is the family of growth factor receptor protein-tyrosine kinases (PTK), such as the epidermal growth factor (EGF) receptor. These receptors have an intrinsic signaling mechanism in which binding of ligand to an external domain activates a cytoplasmic protein kinase domain to phosphorylate target proteins in the mitogenic signal pathway. Approximately half of all known protein-tyrosine kinase genes appear to encode ligand-regulated surface receptors (Table 1).