Bole of protein targeting to glycogen (PTG) in the regulation of protein phosphatase-1 activity

We have recently cloned from 3T3-L1 adipocytes a novel glycogen-tageting subunit of protein phosphatase-1, termed PTG (Printen, 5, A., Brady, M. J., and Saltiel, A. R. (1997) Science 275, 1475-1478), Differentiation of 3T3-L1 fibroblasts into highly insulin-responsive adipocytes resulted in a marked increase: in PTG expression, Immobilized glutathione S-transferase (GST)-PTG fusion protein specifically bound either PP1 or phosphorylase a, Addition of soluble GST-PTG to 3T3-L1. lysates increased PP1 activity against P-32-labeled phosphorylase a by decreasing the K-m of PP1 for phosphorylase 5-fold, while having ma effect on the V-max, of the dephosphorylation reaction, Alternatively, PTG did not affect PP1 activity against hormone-sensitive lipase, PTG was not a direct target of intracellular signaling, as insulin or forskolin treatment of cells did not activate a kinase capable of phosphorylating PTG in vivo or irt vitro, Finally, PTG decreased the ability of DARPP-32 to inhibit PP1 activity from 3T3-L1 adipocyte lysates, These data cumulatively suggest that PTG increases PPI activity against specific proteins by several distinct mechanisms.