PHLPP-1 negatively regulates Akt activity and survival in the heart.
Authors:
Journal: Circulation research
Publication Type: Comparative Study
Date: 2010
DOI: NIHMS242965
ID: 20576936
Abstract
The recently discovered PHLPP-1 (PH domain leucine-rich repeat protein phosphatase-1) selectively dephosphorylates Akt at Ser473 and terminates Akt signaling in cancer cells. The regulatory role of PHLPP-1 in the heart has not been considered.
Chemical List
- Nuclear Proteins|||Proto-Oncogene Proteins c-akt|||PHLPP1 protein, mouse|||Phosphoprotein Phosphatases
Reference List
- Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation. 2000;101:660–667.|||Matsui T, Li L, del Monte F, Fukui Y, Franke TF, Hajjar RJ, Rosenzweig A. Adenoviral gene transfer of activated phosphatidylinositol 3′-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation. 1999;100:2373–2379.|||Craig R, Wagner M, McCardle T, Craig AG, Glembotski CC. The cytoprotective effects of the glycoprotein 130 receptor-coupled cytokine, cardiotrophin-1, require activation of NF-kappa B. J Biol Chem. 2001;276:37621–37629.|||Negoro S, Oh H, Tone E, Kunisada K, Fujio Y, Walsh K, Kishimoto T, Yamauchi-Takihara K. Glycoprotein 130 regulates cardiac myocyte survival in doxorubicin-induced apoptosis through phosphatidylinositol 3-kinase/Akt phosphorylation and Bcl-xL/caspase-3 interaction. Circulation. 2001;103:555–561.|||Miyamoto S, Murphy AN, Brown JH. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ. 2008;15:521–529.|||Cohen MV, Downey JM. Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol. 2008;103:203–215.|||Means CK, Miyamoto S, Chun J, Brown JH. S1P1 receptor localization confers selectivity for Gi-mediated cAMP and contractile responses. J Biol Chem. 2008;283:11954–11963.|||Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307:1098–1101.|||Newton AC. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J. 2003;370:361–371.|||Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–1947.|||Kawase T, Ohki R, Shibata T, Tsutsumi S, Kamimura N, Inazawa J, Ohta T, Ichikawa H, Aburatani H, Tashiro F, Taya Y. PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt. Cell. 2009;136:535–550.|||Padmanabhan S, Mukhopadhyay A, Narasimhan SD, Tesz G, Czech MP, Tissenbaum HA. A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 2009;136:939–951.|||Kuo YC, Huang KY, Yang CH, Yang YS, Lee WY, Chiang CW. Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55α regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt. J Biol Chem. 2008;283:1882–1892.|||Park CH, Kim YS, Kim YH, Choi MY, Yoo JM, Kang SS, Choi WS, Cho GJ. Calcineurin mediates AKT dephosphorylation in the ischemic rat retina. Brain Res. 2008;1234:148–157.|||Gao T, Furnari F, Newton AC. PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell. 2005;18:13–24.|||Brognard J, Sierecki E, Gao T, Newton AC. PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell. 2007;25:917–931.|||Liu J, Weiss HL, Rychahou P, Jackson LN, Evers BM, Gao T. Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis. Oncogene. 2009;28:994–1004.|||Schwartzbauer G, Robbins J. The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival. J Biol Chem. 2001;276:35786–35793.|||Ruan H, Li J, Ren S, Gao J, Li G, Kim R, Wu H, Wang Y. Inducible and cardiac specific PTEN inactivation protects ischemia/reperfusion injury. J Mol Cell Cardiol. 2009;46:193–200.|||Ni YG, Wang N, Cao DJ, Sachan N, Morris DJ, Gerard RD, Kuro OM, Rothermel BA, Hill JA. FoxO transcription factors activate Akt and attenuate insulin signaling in heart by inhibiting protein phosphatases. Proc Natl Acad Sci U S A. 2007;104:20517–20522.|||Masubuchi S, Gao T, O'Neill A, Eckel-Mahan K, Newton AC, Sassone-Corsi P. Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock. Proc Natl Acad Sci U S A. 2010;107:1642–1647.|||Shimizu K, Okada M, Takano A, Nagai K. SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus. FEBS Lett. 1999;458:363–369.|||Gao T, Brognard J, Newton AC. The phosphatase PHLPP controls the cellular levels of protein kinase C. J Biol Chem. 2008;283:6300–6311.|||Wang L, Ma W, Markovich R, Chen JW, Wang PH. Regulation of cardiomyocyte apoptotic signaling by insulin-like growth factor I. Circ Res. 1998;83:516–522.|||Camper-Kirby D, Welch S, Walker A, Shiraishi I, Setchell KD, Schaefer E, Kajstura J, Anversa P, Sussman MA. Myocardial Akt activation and gender: increased nuclear activity in females versus males. Circ Res. 2001;88:1020–1027.|||Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings BA. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 1996;15:6541–6551.|||DeBosch B, Sambandam N, Weinheimer C, Courtois M, Muslin AJ. Akt2 regulates cardiac metabolism and cardiomyocyte survival. J Biol Chem. 2006;281:32841–32851.|||Inagaki K, Begley R, Ikeno F, Mochly-Rosen D. Cardioprotection by ε-protein kinase C activation from ischemia: continuous delivery and antiarrhythmic effect of an ε-protein kinase C-activating peptide. Circulation. 2005;111:44–50.|||Taniyama Y, Walsh K. Elevated myocardial Akt signaling ameliorates doxorubicin-induced congestive heart failure and promotes heart growth. J Mol Cell Cardiol. 2002;34:1241–1247.|||Kwon SH, Pimentel DR, Remondino A, Sawyer DB, Colucci WS. H2O2 regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways. J Mol Cell Cardiol. 2003;35:615–621.|||Pham FH, Sugden PH, Clerk A. Regulation of protein kinase B and 4E-BP1 by oxidative stress in cardiac myocytes. Circ Res. 2000;86:1252–1258.|||Hausenloy DJ, Yellon DM. New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res. 2004;61:448–460.|||Yamashita K, Kajstura J, Discher DJ, Wasserlauf BJ, Bishopric NH, Anversa P, Webster KA. Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1. Circ Res. 2001;88:609–614.|||Berthiaume JM, Wallace KB. Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol Toxicol. 2007;23:15–25.|||Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 2008;88:581–609.|||Lai HC, Liu TJ, Ting CT, Sharma PM, Wang PH. Insulin-like growth factor-1 prevents loss of electrochemical gradient in cardiac muscle mitochondria via activation of PI 3 kinase/Akt pathway. Mol Cell Endocrinol. 2003;205:99–106.|||Lu G, Ren S, Korge P, Choi J, Dong Y, Weiss J, Koehler C, Chen JN, Wang Y. A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Genes Dev. 2007;21:784–796.|||Bijur GN, Jope RS. Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem. 2003;87:1427–1435.|||Kunkel MT, Ni Q, Tsien RY, Zhang J, Newton AC. Spatio-temporal dynamics of protein kinase B/Akt signaling revealed by a genetically encoded fluorescent reporter. J Biol Chem. 2005;280:5581–5587.