EBP50 protein binds to the C-terminus of the beta-2 adrenergic receptor (β2-AR). EBP50 also associates with a complex that connects to actin, thus serving as a link between the cytoskeleton and β2-AR. The β2-AR receptor is eventually endocytosed, where it will either be consigned to a lysosome for degradation or recycled back to the cell membrane. Scientists have demonstrated that when the Ser-411 residue of the β2-AR PDZ binding domain, which interacts directly with EBP50, is phosphorylated, the receptor is degraded. If Ser-411 is left unmodified, the receptor is recycled. The role played by PDZ domains and their binding sites indicate a regulative relevance beyond simply receptor protein localization. PDZ domains are being studied further to better understand the role they play in different signaling pathways. Research has increased as these domains have been linked to different diseases including cancer as discussed above. Regulation of PDZ domain activity PDZ domain function can be both inhibited and activated by various mechanisms. Two of the most prevalent include allosteric interactions and posttranslational modifications. Post-translational modifications The most common post-traslational modification seen on PDZ domains is phosphorylation. This modification is primarily an inhibitor of PDZ domain and ligand activity. In some examples, phosphorylation of amino acid side chains eliminates the ability of the PDZ domain to form hydrogen bonds, disrupting the normal binding patterns. The end result is a loss of PDZ domain function and further signaling. Another way phosphorylation can disrupt regular PDZ domain function is by altering the charge ratio and further affecting binding and signaling. In rare cases researchers have seen post-translational modifications activate PDZ domain activity but these cases are few. Another post-translational modification that can regulate PDZ domains is the formation of disulfide bridges. Many PDZ domains contain cysteines and are susceptible to disulfide bond formation in oxidizing conditions. This modification acts primarily as an inhibitor of PDZ domain function. Allosteric Interactions Protein-protein interactions have been observed to alter the effectiveness of PDZ domains binding to ligands. These studies show that allosteric effects of certain proteins can affect the binding affinity for different substrates. Different PDZ domains can even have this allosteric effect on each other. This PDZ-PDZ interaction only acts as an inhibitor. Other experiments have shown that certain enzymes can enhance the binding of PDZ domains. Researchers found that the protein ezrin enhances the binding of the PDZ protein NHERF1. PDZ proteins PDZ proteins are a