Hormone binding can directly stimulate the protein kinase activity of receptors. The insulin receptor is an example of this type. The small protein insulin binds to its receptor, which crosses the outer membrane of a cell. These proteins have three domains. The extracellular domain of these receptors binds the hormone, the transmembrane domain crosses the membrane, and the intracellular domain is a protein kinase. The activity of the kinase domain is stimulated when the hormone is bound to the receptor. See Figure .
Another protein hormone, epidermal growth factor, is bound to the extracellular domain of its receptor. A mutated form of the receptor, which lacks the hormone‐binding domain, results in the kinase activity being permanently “on.” This leads to cancer because the cell is signaled to grow at all times—the hallmark of cancer.
Responses to various hormones can “cross‐talk” by means of multiple interactions/modifications. One example has already been discussed: Phosphorylase b kinase is responsive both to cAMP and to Ca 2+ ions. Receptors can themselves be phosphorylated by protein kinases, which can change their activity. Thus, a protein kinase may respond to cyclic AMP (for example, through the epinephrine receptor), intracellular calcium ion concentration (through the IP 3 system), and an extracellular hormone such as a growth factor (through the kinase activity of a receptor). All of these activities can reinforce or antagonize each other, providing precise control.