ABSTRACT
Protein phosphorylation is a universal regulatory mechanism and in eukaryotic cells is a pervasive phenomenon that permeates almost every aspect of cell physiology and biochemistry. It is therefore almost impossible to write a book, let alone a single book chapter, that does justice to the subject of protein phosphorylation even in a simple eukaryotic organism such as yeast. In the yeast Saccharomyces cerevisiae as in all eukaryotes, protein phosphorylation plays critical regulatory roles in a large number of cellular processes. This chapter will review selected examples of protein kinases and protein phosphatases where sufficient progress has been made to allow a meaningful overview to be taken, and particularly those instances where the molecular events that have been uncovered can be linked to the physiological responses of the cell. The essence of protein phosphorylation is that by adding a phosphate group to a polypeptide, a protein kinase can modify the biological function of its target. Introduction of a phosphate group can have a variety of effects, including steric blocking and either allosteric or conformational inactivation or activation. A good example of the latter is the activation of some protein kinases by phosphorylation on their activation or T-loop (between subdomains VII and VIII), leading to a conformational change that allows access of the protein kinase to its substrate (Russo et al., 1996; Huse and Kuriyan, 2002). For phosphoregulation to be reversible, it is necessary to be able to remove as well as add the key phosphate groups. Thus is it the balance between the phosphorylation and dephosphorylation of specific residues that controls their phosphorylation state and so, unless there is very rapid protein turnover, phosphoprotein phosphatases are also critical players. Although protein phosphatases have been considered to be rather non-specific enzymes in the past, providing simply a constant background level of dephosphorylation to oppose the protein kinases, it is now accepted that they frequently have highly specific roles to play.
