Post-translational modification phosphorylation

Both ChEs undergo several post-translational modifications, including glycosylation and glycosylphosphatidy-linositolation (GPI), phosphorylation and carbamylation. 

After their synthesis (translation), most proteins go through a maturation process, called post-translational modification that affects their activity. One common post-translational modification of proteins is phosphorylation. Two functional classes of enzymes mediate this reversible process protein kinases add phosphate groups to hydroxyl groups of serine, threonine and tyrosine in their substrate, while protein phosphatases remove phosphate groups. The phosphate-linking... 

Post-translational modification of proteins plays a critical role in cellular function. For, example protein phosphorylation events control the majority of the signal transduction pathways in eukaryotic cells. Therefore, an important goal of proteomics is the identification of post-translational modifications. Proteins can undergo a wide range of post-translational modifications such as phosphorylation, glycosylation, sulphonation, palmitoylation and ADP-ribosylation. These modifications can play an essential role in the function of the protein and mass spectrometry has been used to characterize such modifications. 

As described in more detail below, agonist binding will lead to signaling as well as phosphorylation of Ser and Thr residues, especially, but also, in selected cases, Tyr residues located in intracellular loop-3 and in the C-terminal extension. This post-translational modification alters the affinity of the receptor for various intracellular proteins, including arrestin, which sterically prevents further G-protein binding and functions as an adaptor protein. Also, interaction with other types of scaffolding proteins such as PSD-95-like proteins, is influenced by the phosphorylation state of the receptor. 

In addition to containing protein-protein interaction motifs, E3-substrate specificity may be affected by post-translational modifications. In particular, phosphorylation can alter E3-substrate interactions. One example is p53 where certain phosphorylations inhibit its direct binding to Mdm2, while others indirectly enhance their association by promoting nuclear localization of p53 [104-106]. Phosphorylation also directly enhances substrate interactions, as exemplified by the Cbls, which include phospho-tyrosine binding domains (see below) [107]. 

Proteasome and RC subunits are subjected to a variety of post-translational modifications including phosphorylation, acetylation, myristoylation, and even O-glycosylation [136-140]. In yeast all seven a-subunits are acetylated as well as two yS-subunits. Since acetylation of the N-terminal threonine in an active j8-subunit would poison catalysis, it has been suggested that the propeptide extensions function to prevent acetylation [130]. Three members of the S4 ATPase subfamily (S4,... 

Post-translational modifications, such as phosphorylation, complex glycosylation, and lipidation, typically occur in eukaryotic organisms. Therefore, their expression in prokaryotic systems like Escherichia coli is difficult. However, it should be noted that via clever engineering and coexpression of specific enzymes, access can be granted to specific lipidated proteins via expression in bacteria, for example, via the expression of A -myristoyltransferase in E. coli Eukaryotic systems that can be used for the expression of post-translationally modified proteins are yeast and Dictyostelium discoidum. Furthermore, lipidated proteins, such as the Rah proteins, can be obtained via purification from tissue sources or from membrane fractions of insect cells that had been infected with baculovirus bearing a Rah gene. ... 

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