Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy.
Authors:
Journal: Cardiovascular research
Publication Type: Journal Article
Date: 2015
DOI: PMC4303795
ID: 25411382
Abstract
To examine the role of physiological Akt signalling in pathological hypertrophy through analysis of PHLPP1 (PH domain leucine-rich repeat protein phosphatase) knock-out (KO) mice.
Chemical List
- Nuclear Proteins|||Proto-Oncogene Proteins c-akt|||PHLPP1 protein, mouse|||Phosphoprotein Phosphatases
Reference List
- Kemi OJ, Ceci M, Wisloff U, Grimaldi S, Gallo P, Smith GL, Condorelli G, Ellingsen O. Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy. J Cell Physiol. 2008;214:316–321.|||Catalucci D, Latronico MV, Ellingsen O, Condorelli G. Physiological myocardial hypertrophy: how and why? Front Biosci. 2008;13:312–324.|||Maillet M, van Berlo JH, Molkentin JD. Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol. 2013;14:38–48.|||Dorn GW., II The fuzzy logic of physiological cardiac hypertrophy. Hypertension. 2007;49:962–970.|||Kehat I, Molkentin JD. Molecular pathways underlying cardiac remodeling during pathophysiological stimulation. Circulation. 2010;122:2727–2735.|||van Berlo JH, Maillet M, Molkentin JD. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest. 2013;123:37–45.|||Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol. 1997;59:551–571.|||Sussman MA, Volkers M, Fischer K, Bailey B, Cottage CT, Din S, Gude N, Avitabile D, Alvarez R, Sundararaman B, Quijada P, Mason M, Konstandin MH, Malhowski A, Cheng Z, Khan M, McGregor M. Myocardial AKT: the omnipresent nexus. Physiol Rev. 2011;91:1023–1070.|||Dorn GW, Force T. Protein kinase cascades in the regulation of cardiac hypertrophy. J Clin Invest. 2005;115:527–537.|||Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 2006;7:589–600.|||Condorelli G, Drusco A, Stassi G, Bellacosa A, Roncarati R, Iaccarino G, Russo MA, Gu Y, Dalton N, Chung C, Latronico MV, Napoli C, Sadoshima J, Croce CM, Ross J., Jr Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. Proc Natl Acad Sci USA. 2002;99:12333–12338.|||DeBosch B, Treskov I, Lupu TS, Weinheimer C, Kovacs A, Courtois M, Muslin AJ. Akt1 is required for physiological cardiac growth. Circulation. 2006;113:2097–2104.|||Shioi T, McMullen JR, Kang PM, Douglas PS, Obata T, Franke TF, Cantley LC, Izumo S. Akt/protein kinase B promotes organ growth in transgenic mice. Mol Cell Biol. 2002;22:2799–2809.|||Catalucci D, Latronico MV, Ceci M, Rusconi F, Young HS, Gallo P, Santonastasi M, Bellacosa A, Brown JH, Condorelli G. Akt increases sarcoplasmic reticulum Ca2+ cycling by direct phosphorylation of phospholamban at Thr17. J Biol Chem. 2009;284:28180–28187.|||Latronico MVG, Costinean S, Lavitrano ML, Peschle C, Condorelli G. Regulation of cell size and contractile function by AKT in cardiomyocytes. Ann N Y Acad Sci. 2004;1015:250–260.|||Shiojima I, Schiekofer S, Schneider JG, Belisle K, Sato K, Andrassy M, Galasso G, Walsh K. Short-term Akt activation in cardiac muscle cells improves contractile function in failing hearts. Am J Path. 2012;181:1969–1976.|||Schiekofer S, Belisle K, Galasso G, Schneider JG, Boehm BO, Burster T, Schmitz G, Walsh K. Angiogenic-regulatory network revealed by molecular profiling heart tissue following Akt1 induction in endothelial cells. Angiogenesis. 2008;11:289–299.|||Kitamura T, Asai N, Enomoto A, Maeda K, Kato T, Ishida M, Jiang P, Watanabe T, Usukura J, Kondo T, Costantini F, Murohara T, Takahashi M. Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin. Nat Cell Biol. 2008;10:329–337.|||Karar J, Maity A. PI3K/AKT/mTOR pathway in angiogenesis. Front Mol Neurosci. 2011;4:51.|||Newton AC, Trotman LC. Turning Off AKT: PHLPP as a drug target. Annu Rev Pharmacol Toxicol. 2014;54:537–558.|||Mullonkal CJ, Toledo-Pereyra LH. Akt in ischemia and reperfusion. J Invest Surg. 2007;20:195–203.|||Chen WS, Xu PZ, Gottlob K, Chen ML, Sokol K, Shiyanova T, Roninson I, Weng W, Suzuki R, Tobe K, Kadowaki T, Hay N. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. 2001;15:2203–2208.|||Easton RM, Cho H, Roovers K, Shineman DW, Mizrahi M, Forman MS, Lee VM, Szabolcs M, de Jong R, Oltersdorf T, Ludwig T, Efstratiadis A, Birnbaum MJ. Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Mol Cell Biol. 2005;25:1869–1878.|||Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG, Hay N. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 2003;17:1352–1365.|||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.|||Shimizu K, Okada M, Nagai K, Fukada Y. Suprachiasmatic nucleus circadian oscillatory protein, a novel binding partner of K-Ras in the membrane rafts, negatively regulates MAPK pathway. J Biol Chem. 2003;278:14920–14925.|||Miyamoto S, Purcell NH, Smith JM, Gao T, Whittaker R, Huang K, Castillo R, Glembotski CC, Sussman MA, Newton AC, Brown JH. PHLPP-1 negatively regulates Akt activity and survival in the heart. Circ Res. 2010;107:476–484.|||Gao T, Brognard J, Newton AC. The phosphatase PHLPP controls the cellular levels of protein kinase C. J Biol Chem. 2008;283:6300–6311.|||Liu J, Stevens PD, Li X, Schmidt MD, Gao T. PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth. Mol Cell Biol. 2011;31:4917–4927.|||Qiao M, Wang Y, Xu X, Lu J, Dong Y, Tao W, Stein J, Stein GS, Iglehart JD, Shi Q, Pardee AB. Mst1 is an interacting protein that mediates PHLPPs’ induced apoptosis. Mol Cell. 2010;38:512–523.|||McMullen JR, Shioi T, Huang WY, Zhang L, Tarnavski O, Bisping E, Schinke M, Kong S, Sherwood MC, Brown J, Riggi L, Kang PM, Izumo S. The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway. J Biol Chem. 2004;279:4782–4793.|||Ceci M, Gallo P, Santonastasi M, Grimaldi S, Latronico MV, Pitisci A, Missol-Kolka E, Scimia MC, Catalucci D, Hilfiker-Kleiner D, Condorelli G. Cardiac-specific overexpression of E40K active Akt prevents pressure overload-induced heart failure in mice by increasing angiogenesis and reducing apoptosis. Cell Death Differ. 2007;14:1060–1062.|||Kim YK, Kim SJ, Yatani A, Huang Y, Castelli G, Vatner DE, Liu J, Zhang Q, Diaz G, Zieba R, Thaisz J, Drusco A, Croce C, Sadoshima J, Condorelli G, Vatner SF. Mechanism of enhanced cardiac function in mice with hypertrophy induced by overexpressed Akt. J Biol Chem. 2003;278:47622–47628.|||Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R, Colucci WS, Walsh K. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest. 2005;115:2108–2118.|||Tsujita Y, Muraski J, Shiraishi I, Kato T, Kajstura J, Anversa P, Sussman MA. Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy. Proc Natl Acad Sci USA. 2006;103:11946–11951.|||Rota M, Boni A, Urbanek K, Padin-Iruegas ME, Kajstura TJ, Fiore G, Kubo H, Sonnenblick EH, Musso E, Houser SR, Leri A, Sussman MA, Anversa P. Nuclear targeting of Akt enhances ventricular function and myocyte contractility. Circ Res. 2005;97:1332–1341.|||Catalucci D, Zhang DH, DeSantiago J, Aimond F, Barbara G, Chemin J, Bonci D, Picht E, Rusconi F, Dalton ND, Peterson KL, Richard S, Bers DM, Brown JH, Condorelli G. Akt regulates L-type Ca2+ channel activity by modulating Cavalpha1 protein stability. J Cell Biol. 2009;184:923–933.|||Chen B, Van Winkle JA, Lyden PD, Brown JH, Purcell NH. PHLPP1 gene deletion protects the brain from ischemic injury. J Cereb Blood Flow Metab. 2013;33:196–204.|||Maillet M, Purcell NH, Sargent MA, York AJ, Bueno OF, Molkentin JD. DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem. 2008;283:31246–31255.|||Purcell NH, Wilkins BJ, York A, Saba-El-Leil MK, Meloche S, Robbins J, Molkentin JD. Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo. Proc Natl Acad Sci USA. 2007;104:14074–14079.|||Dusaban SS, Purcell NH, Rockenstein E, Masliah E, Cho MK, Smrcka AV, Brown JH. Phospholipase C links G protein-coupled receptor activation to inflammatory astrocytic responses. Proc Natl Acad Sci USA. 2013;110:3609–3614.|||Huang C, Zhang X, Ramil JM, Rikka S, Kim L, Lee Y, Gude NA, Thistlethwaite PA, Sussman MA, Gottlieb RA, Gustafsson AB. Juvenile exposure to anthracyclines impairs cardiac progenitor cell function and vascularization resulting in greater usceptibility to stress-induced myocardial injury in adult mice. Circulation. 2010;121:675–683.|||Chen M, Pratt CP, Zeeman ME, Schultz N, Taylor BS, O'Neill A, Castillo-Martin M, Nowak DG, Naguib A, Grace DM, Murn J, Navin N, Atwal GS, Sander C, Gerald WL, Cordon-Cardo C, Newton AC, Carver BS, Trotman LC. Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression. Cancer Cell. 2011;20:173–186.|||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.|||Kim J, Wende AR, Sena S, Theobald HA, Soto J, Sloan C, Wayment BE, Litwin SE, Holzenberger M, LeRoith D, Abel ED. Insulin-like growth factor I receptor signaling is required for exercise-induced cardiac hypertrophy. Mol Endo. 2008;22:2531–2543.|||Shiojima I, Walsh K. Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev. 2006;20:3347–3365.|||Park M, Vatner SF, Yan L, Gao S, Yoon S, Lee GJ, Xie LH, Kitsis RN, Vatner DE. Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload. Basic Res Cardiol. 2013;108:324.|||Cittadini A, Monti MG, Iaccarino G, Di Rella F, Tsichlis PN, Di Gianni A, Stromer H, Sorriento D, Peschle C, Trimarco B, Sacca L, Condorelli G. Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling. Gene Ther. 2006;13:8–19.|||Hua Y, Zhang Y, Ceylan-Isik AF, Wold LE, Nunn JM, Ren J. Chronic Akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy. Basic Res Cardiol. 2011;106:1173–1191.|||Cook SA, Matsui T, Li L, Rosenzweig A. Transcriptional effects of chronic Akt activation in the heart. J Biol Chem. 2002;277:22528–22533.|||Duronio V. The life of a cell: apoptosis regulation by the PI3K/PKB pathway. Biochem J. 2008;415:333–344.|||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.|||Jackson TC, Verrier JD, Semple-Rowland S, Kumar A, Foster TC. PHLPP1 splice variants differentially regulate AKT and PKCalpha signaling in hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus. J Neurochem. 2010;115:941–955.|||Li X, Stevens PD, Liu J, Yang H, Wang W, Wang C, Zeng Z, Schmidt MD, Yang M, Lee EY, Gao T. PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice. Gastroenterology. 2014;146:1301–1312. e1301–1310.|||Ackah E, Yu J, Zoellner S, Iwakiri Y, Skurk C, Shibata R, Ouchi N, Easton RM, Galasso G, Birnbaum MJ, Walsh K, Sessa WC. Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis. J Clin Invest. 2005;115:2119–2127.|||Giordano FJ, Gerber HP, Williams SP, VanBruggen N, Bunting S, Ruiz-Lozano P, Gu Y, Nath AK, Huang Y, Hickey R, Dalton N, Peterson KL, Ross J, Jr, Chien KR, Ferrara N. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA. 2001;98:5780–5785.|||Izumiya Y, Shiojima I, Sato K, Sawyer DB, Colucci WS, Walsh K. Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension. 2006;47:887–893.