Phosphoprotein enriched in astrocytes (PEA)-15: A potential therapeutic target in multiple disease states

Pharmacology and Therapeutics

Volumn 143, Issue 3, 2014, Pages 265-274

  Greig, Fiona H ^a   Nixon, Graeme F ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

Apoptosis; Cancer; ERK1 2; PEA 15; Proliferation; Type 2 diabetes

Indexed keywords

CYTOPLASM PROTEIN; FAS ASSOCIATED DEATH DOMAIN PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PHOSPHOPROTEIN ENRICHED IN ASTROCYTES 15; UNCLASSIFIED DRUG; PEA15 PROTEIN, HUMAN; PHOSPHOPROTEIN; SIGNAL PEPTIDE;

APOPTOSIS; ARTICLE; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; COMPLEX FORMATION; HUMAN; NEUROLOGIC DISEASE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; ANIMAL; BRAIN DISEASE; CHEMISTRY; ENDOCRINE DISEASE; METABOLISM; NEOPLASM; PROTEIN CONFORMATION;

ANIMALS; BRAIN DISEASES; CARDIOVASCULAR DISEASES; ENDOCRINE SYSTEM DISEASES; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; NEOPLASMS; PHOSPHOPROTEINS; PROTEIN CONFORMATION;

EID: 84905229949     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2014.03.006     Document Type: Review

References (126)

1. H. Araujo, N. Danziger, J. Cordier, J. Glowinski, and H. Chneiweiss Characterization of PEA-15, a major substrate for protein kinase C in astrocytes J Biol Chem 268 1993 5911 5920
2. C. Bartholomeusz, A.M. Gonzalez-Angulo, A. Kazansky, S. Krishnamurthy, P. Liu, and L.X. Yuan et al. PEA-15 inhibits tumorigenesis in an MDA-MB-468 triple-negative breast cancer xenograft model through increased cytoplasmic localization of activated extracellular signal-regulated kinase Clin Cancer Res 16 2010 1802 1811
3. C. Bartholomeusz, A.M. Gonzalez-Angulo, P. Liu, N. Hayashi, A. Lluch, and J. Ferrer-Lozano et al. High ERK protein expression levels correlate with shorter survival in triple-negative breast cancer patients Oncologist 17 2012 766 774
4. C. Bartholomeusz, H. Itamochi, M. Nitta, H. Saya, M.H. Ginsberg, and N.T. Ueno Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15 Oncogene 25 2006 79 90
5. C. Bartholomeusz, D. Rosen, C. Wei, A. Kazansky, F. Yamasaki, and T. Takahashi et al. PEA-15 induces autophagy in human ovarian cancer cells and is associated with prolonged overall survival Cancer Res 68 2008 9302 9310
6. A.C. Bellail, M.C. Tse, J.H. Song, S. Phuphanich, J.J. Olson, and S.Y. Sun et al. DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas J Cell Mol Med 14 2010 1303 1317
7. J.M. Besterman, V. Duronio, and P. Cuatrecasas Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger Proc Natl Acad Sci U S A 83 1986 6785 6789
8. S. Blum, A.N. Moore, F. Adams, and P.K. Dash A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory J Neurosci 19 1999 3535 3544
9. G. Buchwalter, C. Gross, and B. Wasylyk Ets ternary complex transcription factors Gene 324 2004 1 14
10. R. Buonomo, F. Giacco, A. Vasaturo, S. Caserta, S. Guido, and V. Pagliara et al. PED/PEA-15 controls fibroblast motility and wound closure by ERK1/2-dependent mechanisms J Cell Physiol 227 2012 2106 2116
11. K. Callaway, O. Abramczyk, L. Martin, and K.N. Dalby The anti-apoptotic protein PEA-15 is a tight binding inhibitor of ERK1 and ERK2, which blocks docking interactions at the D-recruitment site Biochemistry 46 2007 9187 9198
12. A. Cassese, G.A. Raciti, F. Fiory, C. Nigro, L. Ulianich, and I. Castano et al. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15 PLoS One 8 2013 e60555
13. R.J. Chang, R.M. Nakamura, H.L. Judd, and S.A. Kaplan Insulin resistance in nonobese patients with polycystic ovarian disease J Clin Endocrinol Metab 57 1983 356 359
14. J.Y. Chang, W. Xia, R. Shao, F. Sorgi, G.N. Hortobagyi, and L. Huang et al. The tumor suppression activity of E1A in HER-2/neu-overexpressing breast cancer Oncogene 14 1997 561 568
15. S.G. Choi, F. Ruf-Zamojski, H. Pincas, B. Roysam, and S.C. Sealfon Characterization of a MAPK scaffolding protein logic gate in gonadotropes Mol Endocrinol 25 2011 1027 1039
16. G. Condorelli, G. Vigliotta, A. Cafieri, A. Trencia, P. Andalo, and F. Oriente et al. PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis Oncogene 18 1999 4409 4415
17. G. Condorelli, G. Vigliotta, C. Iavarone, M. Caruso, C.G. Tocchetti, and F. Andreozzi et al. PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus EMBO J 17 1998 3858 3866
18. G. Condorelli, G. Vigliotta, A. Trencia, M.A. Maitan, M. Caruso, and C. Miele et al. Protein kinase C (PKC)-alpha activation inhibits PKC-zeta and mediates the action of PED/PEA-15 on glucose transport in the L6 skeletal muscle cells Diabetes 50 2001 1244 1252
19. A. Daigeler, L. Klein-Hitpass, M.A. Chromik, O. Muller, J. Hauser, and H.H. Homann et al. Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures BMC Cancer 8 2008 313
20. N. Danziger, M. Yokoyama, T. Jay, J. Cordier, J. Glowinski, and H. Chneiweiss Cellular expression, developmental regulation, and phylogenic conservation of PEA-15, the astrocytic major phosphoprotein and protein kinase C substrate J Neurochem 64 1995 1016 1025
21. K.M. Debatin, and P.H. Krammer Death receptors in chemotherapy and cancer Oncogene 23 2004 2950 2966
22. R.A. DeFronzo, R.C. Bonadonna, and E. Ferrannini Pathogenesis of NIDDM. A balanced overview Diabetes Care 15 1992 318 368
23. A. Dunaif, K.R. Segal, W. Futterweit, and A. Dobrjansky Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome Diabetes 38 1989 1165 1174
24. A. Eckert, B.C. Bock, K.E. Tagscherer, T.L. Haas, K. Grund, and J. Sykora et al. The PEA-15/PED protein protects glioblastoma cells from glucose deprivation-induced apoptosis via the ERK/MAP kinase pathway Oncogene 27 2008 1155 1166
25. S. Efendic, and C.G. Ostenson Hormonal responses and future treatment of non-insulin-dependent diabetes mellitus (NIDDM) J Intern Med 234 1993 127 138
26. D.A. Ehrmann, R.B. Barnes, R.L. Rosenfield, M.K. Cavaghan, and J. Imperial Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome Diabetes Care 22 1999 141 146
27. A. Eramo, R. Pallini, F. Lotti, G. Sette, M. Patti, and M. Bartucci et al. Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction Cancer Res 65 2005 11469 11477
28. A. Estelles, M. Yokoyama, F. Nothias, J.D. Vincent, J. Glowinski, and P. Vernier et al. The major astrocytic phosphoprotein PEA-15 is encoded by two mRNAs conserved on their full length in mouse and human J Biol Chem 271 1996 14800 14806
29. B. Farina, L. Pirone, L. Russo, F. Viparelli, N. Doti, and C. Pedone et al. NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites FEBS J 277 2010 4229 4240
30. C. Festuccia, G.L. Gravina, A.M. D'Alessandro, D. Millimaggi, C. Di Rocco, and V. Dolo et al. Downmodulation of dimethyl transferase activity enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in prostate cancer cells Int J Oncol 33 2008 381 388
31. F. Fiory, P. Formisano, G. Perruolo, and F. Beguinot Frontiers: PED/PEA-15, a multifunctional protein controlling cell survival and glucose metabolism Am J Physiol Endocrinol Metab 297 2009 E592 E601
32. P. Formisano, G. Perruolo, S. Libertini, S. Santopietro, G. Troncone, and G.A. Raciti et al. Raised expression of the antiapoptotic protein ped/pea-15 increases susceptibility to chemically induced skin tumor development Oncogene 24 2005 7012 7021
33. P. Formisano, P. Ragno, A. Pesapane, D. Alfano, A.T. Alberobello, and V.E. Rea et al. PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis J Cell Mol Med 16 2012 1435 1446
34. E. Formstecher, J.W. Ramos, M. Fauquet, D.A. Calderwood, J.C. Hsieh, and B. Canton et al. PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase Dev Cell 1 2001 239 250
35. J.P. Frias, J.G. Yu, Y.T. Kruszynska, and J.M. Olefsky Metabolic effects of troglitazone therapy in type 2 diabetic, obese, and lean normal subjects Diabetes Care 23 2000 64 69
36. V. Funke, J. Lehmann-Koch, M. Bickeboller, A. Benner, K.E. Tagscherer, and K. Grund et al. The PEA-15/PED protein regulates cellular survival and invasiveness in colorectal carcinomas Cancer Lett 335 2013 431 440
37. M. Garofalo, G. Romano, C. Quintavalle, M.F. Romano, F. Chiurazzi, and C. Zanca et al. Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cells to TRAIL-induced apoptosis Int J Cancer 120 2007 1215 1222
38. M.F. Gaumont-Leclerc, U.K. Mukhopadhyay, S. Goumard, and G. Ferbeyre PEA-15 is inhibited by adenovirus E1A and plays a role in ERK nuclear export and Ras-induced senescence J Biol Chem 279 2004 46802 46809
39. J.E. Gawecka, D. Geerts, J. Koster, M.J. Caliva, F.J. Sulzmaier, and J. Opoku-Ansah et al. PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma Int J Cancer 131 2012 1556 1568
40. J.E. Gerich The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity Endocr Rev 19 1998 491 503
41. A. Glading, J.A. Koziol, J. Krueger, and M.H. Ginsberg PEA-15 inhibits tumor cell invasion by binding to extracellular signal-regulated kinase 1/2 Cancer Res 67 2007 1536 1544
42. J.C. Grivel, O. Ivanova, N. Pinegina, P.S. Blank, A. Shpektor, and L.B. Margolis et al. Activation of T lymphocytes in atherosclerotic plaques Arterioscler Thromb Vasc Biol 31 2011 2929 2937
43. F. Han, R.R. Tao, G.S. Zhang, Y.M. Lu, L.L. Liu, and Y.X. Chen et al. Melatonin ameliorates ischemic-like injury-evoked nitrosative stress: involvement of HtrA2/PED pathways in endothelial cells J Pineal Res 50 2011 281 291
44. D. Hanahan, and R.A. Weinberg The hallmarks of cancer Cell 100 2000 57 70
45. D. Hanahan, and R.A. Weinberg Hallmarks of cancer: the next generation Cell 144 2011 646 674
46. C.L. Hanis, E. Boerwinkle, R. Chakraborty, D.L. Ellsworth, P. Concannon, and B. Stirling et al. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2 Nat Genet 13 1996 161 166
47. G.K. Hansson, and A. Hermansson The immune system in atherosclerosis Nat Immunol 12 2011 204 212
48. C. Hao, F. Beguinot, G. Condorelli, A. Trencia, E.G. Van Meir, and V.W. Yong et al. Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells Cancer Res 61 2001 1162 1170
49. S. Heikaus, T. Kempf, C. Mahotka, H.E. Gabbert, and U. Ramp Caspase-8 and its inhibitors in RCCs in vivo: the prominent role of ARC Apoptosis 13 2008 938 949
50. J.M. Hill, H. Vaidyanathan, J.W. Ramos, M.H. Ginsberg, and M.H. Werner Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain EMBO J 21 2002 6494 6504
51. P.N. Hopkins Molecular biology of atherosclerosis Physiol Rev 93 2013 1317 1542
52. I. Hunter, K.S. Mascall, J.W. Ramos, and G.F. Nixon A phospholipase Cgamma1-activated pathway regulates transcription in human vascular smooth muscle cells Cardiovasc Res 90 2011 557 564
53. M. Incoronato, M. Garofalo, L. Urso, G. Romano, C. Quintavalle, and C. Zanca et al. miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED Cancer Res 70 2010 3638 3646
54. S. Iovino, F. Oriente, G. Botta, S. Cabaro, V. Iovane, and O. Paciello et al. PED/PEA-15 induces autophagy and mediates TGF-beta1 effect on muscle cell differentiation Cell Death Differ 19 2012 1127 1138
55. D. Jones, C. Morgan, and S. Cockcroft Phospholipase D and membrane traffic. Potential roles in regulated exocytosis, membrane delivery and vesicle budding Biochim Biophys Acta 1439 1999 229 244
56. C.R. Kahn Banting lecture. Insulin action, diabetogenes, and the cause of type II diabetes Diabetes 43 1994 1066 1084
57. K. Kawai-Kowase, and G.K. Owens Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells Am J Physiol Cell Physiol 292 2007 C59 C69
58. K. Kim, M.J. Fisher, S.Q. Xu, and W.S. el-Deiry Molecular determinants of response to TRAIL in killing of normal and cancer cells Clin Cancer Res 6 2000 335 346
59. M. Kishimoto, H. Sakura, K. Hayashi, Y. Akanuma, Y. Yazaki, and M. Kasuga et al. Detection of mutations in the human insulin gene by single strand conformation polymorphisms J Clin Endocrinol Metab 74 1992 1027 1031
60. D. Kitsberg, E. Formstecher, M. Fauquet, M. Kubes, J. Cordier, and B. Canton et al. Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis J Neurosci 19 1999 8244 8251
61. B.E. Klein, R. Klein, S.E. Moss, and K.J. Cruickshanks Parental history of diabetes in a population-based study Diabetes Care 19 1996 827 830
62. P.O. Koh Ferulic acid prevents the cerebral ischemic injury-induced decreases of astrocytic phosphoprotein PEA-15 and its two phosphorylated forms Neurosci Lett 511 2012 101 105
63. J. Krueger, F.L. Chou, A. Glading, E. Schaefer, and M.H. Ginsberg Phosphorylation of phosphoprotein enriched in astrocytes (PEA-15) regulates extracellular signal-regulated kinase-dependent transcription and cell proliferation Mol Biol Cell 16 2005 3552 3561
64. M. Kubes, J. Cordier, J. Glowinski, J.A. Girault, and H. Chneiweiss Endothelin induces a calcium-dependent phosphorylation of PEA-15 in intact astrocytes: identification of Ser104 and Ser116 phosphorylated, respectively, by protein kinase C and calcium/calmodulin kinase II in vitro J Neurochem 71 1998 1307 1314
65. Y. Kuramitsu, H. Miyamoto, T. Tanaka, X. Zhang, M. Fujimoto, and K. Ueda et al. Proteomic differential display analysis identified upregulated astrocytic phosphoprotein PEA-15 in human malignant pleural mesothelioma cell lines Proteomics 9 2009 5078 5089
66. J. Lee, C. Bartholomeusz, S. Krishnamurthy, P. Liu, H. Saso, and T.A. Lafortune et al. PEA-15 unphosphorylated at both serine 104 and serine 116 inhibits ovarian cancer cell tumorigenicity and progression through blocking beta-catenin Oncogenesis 1 2012 e22
67. P.D. Mace, Y. Wallez, M.F. Egger, M.K. Dobaczewska, H. Robinson, and E.B. Pasquale et al. Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK Nat Commun 4 2013 1681
68. M.M. Mahtani, E. Widen, M. Lehto, J. Thomas, M. McCarthy, and J. Brayer et al. Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families Nat Genet 14 1996 90 94
69. S.O. Marx, H. Totary-Jain, and A.R. Marks Vascular smooth muscle cell proliferation in restenosis Circ Cardiovasc Interv 4 2011 104 111
70. S. Menard, E. Tagliabue, and M.I. Colnaghi The 67 kDa laminin receptor as a prognostic factor in human cancer Breast Cancer Res Treat 52 1998 137 145
71. C. Miele, G.A. Raciti, A. Cassese, C. Romano, F. Giacco, and F. Oriente et al. PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells Diabetes 56 2007 622 633
72. S.C. Mizrak, F. Renault-Mihara, M. Parraga, J. Bogerd, H.J. van de Kant, and P.P. Lopez-Casas et al. Phosphoprotein enriched in astrocytes-15 is expressed in mouse testis and protects spermatocytes from apoptosis Reproduction 133 2007 743 751
73. M. Mourtada-Maarabouni, and G.T. Williams Protein phosphatase 4 regulates apoptosis in leukemic and primary human T-cells Leuk Res 33 2009 1539 1551
74. J.J. Nolan, B. Ludvik, P. Beerdsen, M. Joyce, and J. Olefsky Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone N Engl J Med 331 1994 1188 1193
75. R.J. Norman, D. Dewailly, R.S. Legro, and T.E. Hickey Polycystic ovary syndrome Lancet 370 2007 685 697
76. F. Oriente, S. Iovino, A. Cassese, C. Romano, C. Miele, and G. Troncone et al. Overproduction of phosphoprotein enriched in diabetes (PED) induces mesangial expansion and upregulates protein kinase C-beta activity and TGF-beta1 expression Diabetologia 52 2009 2642 2652
77. H. Otani The role of nitric oxide in myocardial repair and remodeling Antioxid Redox Signal 11 2009 1913 1928
78. G.K. Owens, M.S. Kumar, and B.R. Wamhoff Molecular regulation of vascular smooth muscle cell differentiation in development and disease Physiol Rev 84 2004 767 801
79. F. Panariello, G. Perruolo, A. Cassese, F. Giacco, G. Botta, and A.P. Barbagallo et al. Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance J Cell Physiol 227 2012 1485 1492
80. S. Pastorino, H. Renganathan, M.J. Caliva, E.L. Filbert, J. Opoku-Ansah, and F.J. Sulzmaier et al. The death effector domain protein PEA-15 negatively regulates T-cell receptor signaling FASEB J 24 2010 2818 2828
81. J.W. Peacock, J. Palmer, D. Fink, S. Ip, E.M. Pietras, and A.L. Mui et al. PTEN loss promotes mitochondrially dependent type II Fas-induced apoptosis via PEA-15 Mol Cell Biol 29 2009 1222 1234
82. J.W. Ramos The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells Int J Biochem Cell Biol 40 2008 2707 2719
83. J.W. Ramos, T.K. Kojima, P.E. Hughes, C.A. Fenczik, and M.H. Ginsberg The death effector domain of PEA-15 is involved in its regulation of integrin activation J Biol Chem 273 1998 33897 33900
84. J.W. Ramos, D.A. Townsend, D. Piarulli, S. Kolata, K. Light, and G. Hale et al. Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities BMC Neurosci 10 2009 134
85. W. Reardon, R.J. Ross, M.G. Sweeney, L.M. Luxon, M.E. Pembrey, and A.E. Harding et al. Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA Lancet 340 1992 1376 1379
86. F. Renault, E. Formstecher, I. Callebaut, M.P. Junier, and H. Chneiweiss The multifunctional protein PEA-15 is involved in the control of apoptosis and cell cycle in astrocytes Biochem Pharmacol 66 2003 1581 1588
87. F. Renault-Mihara, F. Beuvon, X. Iturrioz, B. Canton, S. De Bouard, and N. Leonard et al. Phosphoprotein enriched in astrocytes-15 kDa expression inhibits astrocyte migration by a protein kinase C delta-dependent mechanism Mol Biol Cell 17 2006 5141 5152
88. H. Renganathan, H. Vaidyanathan, A. Knapinska, and J.W. Ramos Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK to FADD Biochem J 390 2005 729 735
89. M.A. Rizzo, K. Shome, S.C. Watkins, and G. Romero The recruitment of Raf-1 to membranes is mediated by direct interaction with phosphatidic acid and is independent of association with Ras J Biol Chem 275 2000 23911 23918
90. R. Roskoski Jr. ERK1/2 MAP kinases: structure, function, and regulation Pharmacol Res 66 2012 105 143
91. S. Savastano, F. Orio Jr., S. Palomba, T. Cascella, F. Manguso, and G.A. Lupoli et al. Overexpression of the phosphoprotein enriched in diabetes gene product (Ped/pea-15) in women with polycystic ovary syndrome Clin Endocrinol (Oxf) 67 2007 557 562
92. S. Savastano, R. Valentino, C. Di Somma, F. Orio, C. Pivonello, and F. Passaretti et al. Serum 25-hydroxyvitamin D levels, phosphoprotein enriched in diabetes gene product (PED/PEA-15) and leptin-to-adiponectin ratio in women with PCOS Nutr Metab (Lond) 8 2011 84
93. S. Savastano, R. Valentino, G. Pizza, A. De Rosa, F. Orio, and F. Passaretti et al. Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome J Endocrinol Invest 33 2010 446 450
94. A. Sharif, B. Canton, M.P. Junier, and H. Chneiweiss PEA-15 modulates TNFalpha intracellular signaling in astrocytes Ann N Y Acad Sci 1010 2003 43 50
95. A. Sharif, F. Renault, F. Beuvon, R. Castellanos, B. Canton, and L. Barbeito et al. The expression of PEA-15 (phosphoprotein enriched in astrocytes of 15 kDa) defines subpopulations of astrocytes and neurons throughout the adult mouse brain Neuroscience 126 2004 263 275
96. M.D. Siegelin, A. Habel, and T. Gaiser Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma Neurosci Lett 448 2008 161 165
97. G. Stassi, M. Garofalo, M. Zerilli, L. Ricci-Vitiani, C. Zanca, and M. Todaro et al. PED mediates AKT-dependent chemoresistance in human breast cancer cells Cancer Res 65 2005 6668 6675
98. F. Sulzmaier, J. Opoku-Ansah, and J.W. Ramos Phosphorylation is the switch that turns PEA-15 from tumor suppressor to tumor promoter Small GTPases 3 2012 173 177
99. F.J. Sulzmaier, M.K. Valmiki, D.A. Nelson, M.J. Caliva, D. Geerts, and M.L. Matter et al. PEA-15 potentiates H-Ras-mediated epithelial cell transformation through phospholipase D Oncogene 31 2012 3547 3560
100. J.H. Sung, E.H. Cho, W. Min, M.J. Kim, M.O. Kim, and E.J. Jung et al. Identification of proteins regulated by estradiol in focal cerebral ischemic injury - a proteomics approach Neurosci Lett 477 2010 66 71
101. M. Takano, K. Maekura, M. Otani, K. Sano, T. Nakamura-Hirota, and S. Tokuyama et al. Proteomic analysis of the brain tissues from a transgenic mouse model of amyloid beta oligomers Neurochem Int 61 2012 347 355
102. B.K. Tan, J. Chen, R. Adya, and H.S. Randeva Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in omental adipose tissue of women with the polycystic ovary syndrome: ex vivo regulation of ped/pea-15 by glucose, insulin and metformin Diabetes Obes Metab 13 2011 181 184
103. L.A. Thomason, L.J. Smithson, L.N. Hazrati, J. McLaurin, and M.D. Kawaja Reactive astrocytes associated with plaques in TgCRND8 mouse brain and in human Alzheimer brain express phosphoprotein enriched in astrocytes (PEA-15) FEBS Lett 587 2013 2448 2454
104. M. Todaro, Y. Lombardo, M.G. Francipane, M.P. Alea, P. Cammareri, and F. Iovino et al. Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4 Cell Death Differ 15 2008 762 772
105. M. Todaro, M. Zerilli, L. Ricci-Vitiani, M. Bini, M. Perez Alea, and A. Maria Florena et al. Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth of thyroid cancer cells Cancer Res 66 2006 1491 1499
106. A. Trencia, A. Perfetti, A. Cassese, G. Vigliotta, C. Miele, and F. Oriente et al. Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action Mol Cell Biol 23 2003 4511 4521
107. K. Tse, H. Tse, J. Sidney, A. Sette, and K. Ley T cells in atherosclerosis Int Immunol 25 2013 615 622
108. E.C. Twomey, and Y. Wei High-definition NMR structure of PED/PEA-15 death effector domain reveals details of key polar side chain interactions Biochem Biophys Res Commun 424 2012 141 146
109. P. Ungaro, P. Mirra, F. Oriente, C. Nigro, M. Ciccarelli, and V. Vastolo et al. Peroxisome proliferator-activated receptor-gamma activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1 J Biol Chem 287 2012 42951 42961
110. P. Ungaro, R. Teperino, P. Mirra, A. Cassese, F. Fiory, and G. Perruolo et al. Molecular cloning and characterization of the human PED/PEA-15 gene promoter reveal antagonistic regulation by hepatocyte nuclear factor 4alpha and chicken ovalbumin upstream promoter transcription factor II J Biol Chem 283 2008 30970 30979
111. P. Ungaro, R. Teperino, P. Mirra, M. Longo, M. Ciccarelli, and G.A. Raciti et al. Hepatocyte nuclear factor (HNF)-4alpha-driven epigenetic silencing of the human PED gene Diabetologia 53 2010 1482 1492
112. H. Vaidyanathan, J. Opoku-Ansah, S. Pastorino, H. Renganathan, M.L. Matter, and J.W. Ramos ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15 Proc Natl Acad Sci U S A 104 2007 19837 19842
113. R. Valentino, G.A. Lupoli, G.A. Raciti, F. Oriente, E. Farinaro, and E. Della Valle et al. The PEA15 gene is overexpressed and related to insulin resistance in healthy first-degree relatives of patients with type 2 diabetes Diabetologia 49 2006 3058 3066
114. M.G. Valmiki, and J.W. Ramos Death effector domain-containing proteins Cell Mol Life Sci 66 2009 814 830
115. G. Vigliotta, C. Miele, S. Santopietro, G. Portella, A. Perfetti, and M.A. Maitan et al. Overexpression of the ped/pea-15 gene causes diabetes by impairing glucose-stimulated insulin secretion in addition to insulin action Mol Cell Biol 24 2004 5005 5015
116. F. Viparelli, A. Cassese, N. Doti, F. Paturzo, D. Marasco, and N.A. Dathan et al. Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells J Biol Chem 283 2008 21769 21778
117. Y. Watanabe, F. Yamasaki, Y. Kajiwara, T. Saito, T. Nishimoto, and C. Bartholomeusz et al. Expression of phosphoprotein enriched in astrocytes 15 kDa (PEA-15) in astrocytic tumors: a novel approach of correlating malignancy grade and prognosis J Neurooncol 100 2010 449 457
118. C. Xiao, B.F. Yang, N. Asadi, F. Beguinot, and C. Hao Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells J Biol Chem 277 2002 25020 25025
119. X. Xie, C. Bartholomeusz, A.A. Ahmed, A. Kazansky, L. Diao, and K.A. Baggerly et al. Bisphosphorylated PEA-15 sensitizes ovarian cancer cells to paclitaxel by impairing the microtubule-destabilizing effect of SCLIP Mol Cancer Ther 12 2013 1099 1111
120. W. Yu, W.J. Fantl, G. Harrowe, and L.T. Williams Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK Curr Biol 8 1998 56 64
121. Z. Yu, J. Liu, S. Guo, C. Xing, X. Fan, and M. Ning et al. Neuroglobin-overexpression alters hypoxic response gene expression in primary neuron culture following oxygen glucose deprivation Neuroscience 162 2009 396 403
122. D. Yu, J.K. Wolf, M. Scanlon, J.E. Price, and M.C. Hung Enhanced c-erbB-2/neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A Cancer Res 53 1993 891 898
123. C. Zabel, D. Sagi, A.M. Kaindl, N. Steireif, Y. Klare, and L. Mao et al. Comparative proteomics in neurodegenerative and non-neurodegenerative diseases suggest nodal point proteins in regulatory networking J Proteome Res 5 2006 1948 1958
124. C. Zanca, F. Cozzolino, C. Quintavalle, S. Di Costanzo, L. Ricci-Vitiani, and M. Santoriello et al. PED interacts with Rac1 and regulates cell migration/invasion processes in human non-small cell lung cancer cells J Cell Physiol 225 2010 63 72
125. C. Zanca, M. Garofalo, C. Quintavalle, G. Romano, M. Acunzo, and P. Ragno et al. PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer J Cell Mol Med 12 2008 2416 2426
126. Y. Zhang, O. Redina, Y.M. Altshuller, M. Yamazaki, J. Ramos, and H. Chneiweiss et al. Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them J Biol Chem 275 2000 35224 35232