Phosphatases reversibility

In addition to the displacement of caldesmon, smooth muscle cell contraction requires kinase-induced phosphorylation of myosin. Smooth muscle has a unique type of myosin filament called p-light chains which are the target (substrate) for MLCK, but MLCK is only active when complexed with CaCM. Myosin light chain phosphatase reverses the PKA-mediated process and when cytosolic calcium ion concentration falls, CDM is released from CaCM and re-associates with the actin. The central role of calcium-calmodulin in smooth muscle contraction is shown in Figure 7.4. 

FIGURE 20-27 Regulation of sucrose phosphate synthase by phosphorylation. A protein kinase (SPS kinase) specific for sucrose phosphate synthase (SPS) phosphorylates a Ser residue in SPS, inactivating it a specific phosphatase (SPS phosphatase) reverses this inhibition. The kinase is inhibited allosterically by glucose 6-phosphate, which also activates SPS allosterically. The phosphatase is inhibited by Pi, which also inhibits SPS directly. Thus when the concentration of glucose 6-phosphate is high as a result of active photosynthesis, SPS is activated and produces sucrose phosphate. A high P, concentration, which occurs when photosynthetic conversion of ADP to ATP is slow, inhibits sucrose phosphate synthesis. 

PP2C A large family of protein phosphatases. Reverses stress-induced, SAP kinase phosphorylation cascades... 

The acceptors in protein phosphorylation reactions are located inside cells, where the phosphoryl-group donor ATP is abundant. Proteins that are entirely extracellular are not regulated by reversible phosphorylation. Table 10.2 lists a few of the knovm protein kinases. Protein phosphatases reverse the effects of kinases by catalyzing the hydrolytic removal of phosphoryl groups attached to proteins. 

Protem phosphatases reverse the effects of kinases by catalyzing the removal of phosphoryl groups attached to proteins. The enzyme hydrolyzes the bond attaching the phosphoryl group. 

Musc/skel 580 M 1,270 M (bone incr alkaline phosphatase, reversible) ... 

The phenomenon is called desensitization or adaptation. It allows the system to adapt to a given level of hormone so that it can respond to changes in hormone concentrations rather than to absolute amounts. Desensitization is effected by phosphorylation by 3-adrenergic receptor kinase at multiple seine and threonine sites on the carboxyl-terminal region of the P-adrenergic receptor when it has epinephrine bound to it. These covalent modifications of the hormone-receptor complex allow P-arrestin to bind it and further inhibit, but not completely prevent, the GDP-GTP exchange. These events thereby decrease the activation of adenylate cyclase. However, the desensitized receptor can still respond to an increase in epinephrine concentrations. Ultimately, a phosphatase reverses the effects of the modification and resensitizes the receptor. 

Phosphorylation of the tyrosine residues on growth factor receptors and activation of Ras are both short-lived events. Phos-phoprotein phosphatases reverse the phosphorylation, and the GTP bound to Ras is rapidly hydrolyzed to GDP when a GAP (see Solved Problem 6.11) binds to Ras. Therefore, transducing these short-lived signals into longer-lived serine/threonine phosphorylations on MEK and MAP kinases allows the signal, which is initiated by binding of a growth factor to its receptor, to persist. The selection of a particular pathway is achieved at the level of the MAP kinases these are inactive unless they are phosphorylated on specific serine and tyrosine residues, and the only known substrates for MAP kinase kinases are MAP kinases. 

Protein phosphatases are ubiquitous. They are foxmd in all tissues and across species as diverse as mammals, plants, and bacteria, and they play a critical role in the regulation of multiple cellular metabolic pathways. Protein phosphatases reverse tiie active state of kinases through the hydrolytic removal of tiie phosphoryl group from kinases. The protein phosphatases inhibited by microcystins have broad substrate specificity and play roles in the regulation of a wide range of cellular fxmc-tions. Protein phosphatase 2A is highly conserved and is a major downregulator of active protein kinases in eukaryotic cells. Toxic effects in hepatocytes and other... 

---