One common denominator in signal transductions—whether they involve adenylate cyclase, a transmembrane receptor-tyrosine kinase, phospholipase C, or an ion channel—is the eventual regulation of the activity of a protein kinase. We have seen examples of kinases activated by cAMP, insulin, Ca2+/calmodulin, Ca2+/diacylglycerol, and by phosphorylation catalyzed by another protein kinase. The number of known protein kinases has grown remarkably since their discovery by Edwin G. Krebs and Edmond H. Fischer in 1959. Hundreds of different protein kinases, each with its own specific activator and its own specific protein target(s), may be present in eukaryotic cells. Although many other types of covalent modifications are known to occur on proteins, it is clear that phosphorylations make up the vast majority of known regulatory modifications of proteins.
The addition of a phosphate group to a Ser, Thr, or Tyr residue introduces a bulky, highly charged group into a region that was only moderately polar. When the modified side chain is located in a region of the protein critical to its three-dimensional structure, phosphorylation can be expected to have dramatic effects on protein conformation and thus on the catalytic activity of the protein. As a result of evolution, the kinase-phosphorylated Ser, Thr, and/or Tyr residues of regulated proteins occur within common structural motifs (consensus sequences) that are recognized by their specific protein kinases (Table 22-9).
Lehninger-Nelson-Cox: Principles of Biochemistry, 777.o.
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