Glycogen synthase regulation protein phosphatase

Protein phosphatase-1 (Mg +/ATP-dependent phosphatase multisubstrate protein phosphatase M.W. of catalytic subunit is 35,000 major enzyme in regulation of glycogen metabolism in skeletal muscle dephosphorylates glycogen phosphorylase, jS-subunit of phosphorylase kinase, and at least three sites of glycogen synthase regulated by inhibitor-1, inhibitor-2, and GSK-3 -t- Mg +- ATP). 

In contrast to inhibitor 1, DARPP-32 and NIPP1, which regulate signal transduction, the function of inhibitor 2 appears to be different. There is evidence that inhibitor 2 associates with PP1, as the phosphatase is newly synthesized and contributes to the proper folding of the enzyme [40]. Inhibitor 2 can thus be considered a chaperone protein. The inactive PP 1-inhibitor 2 complex can then be activated upon phosphorylation of inhibitor 2 by glycogen synthase kinase-3. Whether this process is regulated in neurons in association with synaptic activity remains unknown. 

Figure 18.14 Glycogen biosynthesis and degradation regulation. cAMP activates cAMP-dependent protein kinases. They cause the phosphorylation of glycogen synthase (inactivation), phosphorylase kinase (activation), and the inhibitory protein. The last inhibits phosphoprotein phosphatase. Activated phosphorylase kinase causes the phosphorylation of phosphorylase b, thus activating it to phosphorylase a. Phosphoprotein phosphatase is inhibited by the phosphorylated inhibitor protein. Such inhibition is released when the inhibitor protein is dephosphorylated. The phosphatase then reactivates glycogen synthase and inactivates phosphorylase kinase and phosphorylase a.

Protein phosphatase-2C (monomer M.W. 43,000 represents a small fraction of glycogen synthase phosphatase in skeletal muscle may primarily regulate other metabolic pathway in vivo). 

Dephosphorylation of glycogen synthase and glycogen phosphorylase reverses the effects of phosphorylation. This converts glycogen synthase to the independent form and glycogen phosphorylase to a less active form. The primary enzyme responsible for dephosphorylating the glycogen metabolism enzymes is phosphoprotein phosphatase (PP-1). It is regulated by another protein called phosphoprotein phosphatase inhibitor (PI-1). PI-1 is also phosphorylated by active protein kinase. When phosphorylated, PI-1 inhibits PP-1. 

---