Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C-kinase-activated PP1 inhibitors.
The regulatory circuit controlling cellular protein phosphatase-1 (PP1), an abundant group of Ser/Thr phosphatases, involves phosphorylation of PP1-specific inhibitor proteins. Malfunctions of these inhibitor proteins have been linked to a variety of diseases, including cardiovascular disease and cancer. Upon phosphorylation at Thr(38), the 17-kDa PP1 inhibitor protein, CPI-17, selectively inhibits a specific form of PP1, myosin light chain phosphatase, which transduces multiple kinase signals into the phosphorylation of myosin II and other proteins. Here, the mechanisms underlying PP1 inhibition and the kinase/PP1 cross-talk mediated by CPI-17 and its related proteins, PHI, KEPI, and GBPI, are discussed.
Department of Molecular Physiology and Biophysics and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. masumi.eto@jefferson.edu
Masumi
M
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D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; C107507:PPP1R14A protein, human; C454464:PPP1R14C protein, human; C480492:PPP1R14D protein, human; D011506:Proteins; D017476:Receptors, Neuropeptide Y; C109491:neuropeptide Y4 receptor; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D043263:Myosin-Light-Chain Phosphatase; D024462:Myosin Type II