Dephosphorylation of proteins

The major determinant of myocardial redox status is the glutathione content of the heart (Griffith and Meister, 1979). Therefore, fluctuations in myocardial glutathione status may exert a regulatory role in cellular metabolism in a comparable manner to the phosphorylation and dephosphorylation of proteins and enzymes. 

Observations from various systems, including yeast, suggest that phosphorylation and dephosphorylation of proteins play important roles in the mitotic and meiotic cell cycles and the differentiation of germ cells. Extracts from mitotic HeLa cells contained phosphoproteins also present in other mitotic and meiotic cell types, but not in interphase cells (Davis et al., 1983). Exposure of Xenopus oocytes to progesterone results in a burst of protein phosphorylation shortly before GVBD (Mailer et al.,... 

Protein phosphatase I that has dissociated from glycogen may be inactivated by association with inhibitor proteins, preventing undesired dephosphorylation of proteins in the cytosol. The activity of inhibitor proteins may in turn be controlled by reversible phosphorylation. A hormone-induced activation of protein kinase A leads to phosphorylation of inhibitor protein 1 the phosphorylated form is the active form of the inhibitor. This mechanism ensures that stimulation of protein phosphorylation mediated by cAMP and protein kinase A is not weakened by an opposing dephosphorylation (Fig. 7.17). 

Protein phosphorylation may be used to switch enzyme activities on and off. The same is true for dephosphorylation of enzymes. In the cell, we often find phosphorylation cascades in which several phosphorylation reactions are connected to one another. Dephosphorylation reactions may also be elements of these cascades. Furthermore, networks of phosphorylation and dephosphorylation of proteins exist which permit the cell to respond to external stimuli in a finely tuned way. 

Dephosphorylation of proteins The phosphate groups added to proteins by protein kinases are removed by protein phosphatases—enzymes that hydrolytically cleave phosphate esters (see Figure 8.8). This ensures that changes in enzymic activity induced by protein phosphorylation are not permanent. 

Protein phosphorylation alters protein ligand binding and/or catalytic functions and hence specific cellular processes, this representing the cellular response to the stimulus of the original primary messenger . The signalling system must be reversible and the protein phosphorylation step of the stimulus-response pathway is reversed through the action of phosphoprotein phosphatases (PPs), which are phosphohydrolases that catalyse the hydrolytic dephosphorylation of proteins ... 

Dephosphorylation of protein-bound phosphates is catalyzed by specific protein phosphatases which transfer phosphate groups, covalently bound to tyrosine-OH- or to serine /threonine OH-groups to H2O. 

The book finishes with five chapters dedicated to protein phosphatases. In Chapter 13, Lutz Tautz presents a comprehensive review of the structure and function of protein tyrosine phosphatases (FTP) to introduce efforts to screen for modulators of PTPs (Chapter 14) and then to use those modulators in an exploration ofT cell receptor signaling (Chapter 15). Finally, Professor Bollen discusses interactor-guided dephosphorylation of protein phosphatase-1 (Chapter 16), while Professor Janssens discusses the structure, regulation, and pharmacological modulation of protein phosphatase 2A (Chapter 17). 

In the liver increased cAMP, via the cAMP-dependent protein kinase, increases gluconeogenesis and dephosphorylation of proteins causes a decrease in gluconeogenesis. 

Other work on ethylene developmental responses using a number of inhibitors of protein kinases and phosphoprotein phosphatases indicates that both these processes are involved in ethylene transduction processes [45-48]. Caution is necessary in interpreting such results however, since it is unlikely that effects on phosphorylation cascades are unique to ethylene. Nevertheless, recent work by Kim et al. [49] has shown that in mung beans, while ethylene induced an increase in ACC oxidase mRNA, it suppressed that for ACC synthase. However, staurosporine and okadaic acid reversed both of these processes, indicating that both phosphorylation and dephosphorylation of proteins is necessary for the signalling processes which regulate these genes. 

The phosphorylation and dephosphorylation of proteins and enzymes are important processes in intracellular regulation. The dephosphorylation of phosphoserine and phosphothreonine residues in proteins is catalyzed by protein phosphatases that... 

Meier R, Thelen M, Hemmings BA. Inactivation and dephosphorylation of protein kinase Balpha (PKBalpha) promoted by hyperosmotic stress. EMBO J 1998 17 7294-7303. 

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