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-dependent form of type 1 serine/threonine protein phosphatase and its phosphorylation at Thr-72 by glycogen synthase kinase-3 results in phosphatase activation. Activation of cytosolic type 1 phosphatase has been observed in cells treated with growth factors. Reported here is the phosphorylation and activation of the ATP-Mg-dependent phosphatase by mitogen-activated protein kinase (MAPK). Recombinant I-2 was phosphorylated by activated MAPK to an extent (approximately 0.3 mol of phosphate/mol 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 activation of phosphatase. Incubation of MAPK with purified ATP-Mg-dependent phosphatase resulted in phosphorylation of the I-2 component and activation of the phosphatase. Ribosomal S6 protein kinase II (p90rsk) was also able to phosphorylate the recombinant I-2; however, this phosphorylation occurred on serines and had no effect on phosphatase activation. Our data may explain growth factor-induced activation of the ATP-Mg-dependent phosphatase and suggest that MAPK may of cytosolic type 1 phosphatase in response to insulin and/or other growth factors.
Wang
Q M
QM
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202-5122, USA.
Guan
K L
KL
Roach
P J
PJ
DePaoli-Roach
A A
AA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011817:Rabbits; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction
D000596:Amino Acids; D000255:Adenosine Triphosphate; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases; D010765:Phosphorylase Phosphatase