PHOSPHORYLATION AND ACTIVATION OF THE ATP-MG-DEPENDENT PROTEIN PHOSPHATASE BY THE MITOGEN-ACTIVATED PROTEIN-KINASE

Inhibitor-2 (I-2) is the regulatory subunit of the cytosolic ATP-Mg-de pendent form of type 1 serine/threonine protein phosphatase and its ph osphorylation at Thr-72 by glycogen synthase kinase-3 results in phosp hatase activation. Activation of cytosolic type 1 phosphatase has been observed in cells treated with growth factors. Reported here is the p hosphorylation and activation of the ATP-Mg-dependent phosphatase by m itogen-activated protein kinase (MAPR). Recombinant I-2 was phosphoryl ated by activated MAPK to an extent (similar to 0.3 mol of phosphate/m ol of polypeptide) similar to that reported for phosphorylation by the alpha isoform of glycogen synthase kinase-3. The phosphorylation of I -2 by MAPK was exclusively at Thr-72, the site involved in the activat ion of phosphatase. Incubation of MAPK with purified ATP Mg-dependent phosphatase resulted in phosphorylation of the I-2 component and activ ation of the phosphatase. Ribosomal S6 protein kinase II (p9O(rsh)) wa s also able to phosphorylate the recombinant I-2; however, this phosph orylation occurred on serines and had no effect on phosphatase activat ion. Our data may explain growth factor-induced activation of the ATP- Mg-dependent phosphatase and suggest that MAPK may be the physiologica l kinase responsible for the activation of cytosolic type 1 phosphatas e in response to insulin and/or other growth factors.