γ-Secretase: A multifaceted regulator of angiogenesis: Angiogenesis Review Series

Journal of Cellular and Molecular Medicine

Volumn 12, Issue 3, 2008, Pages 781-795

  Boulton, Michael E ^a,b   Cai, Jun ^a   Grant, Maria B ^b  

^a UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

secretase; Amyloid; Angiogenesis; Notch; Presenilin; Receptor translocation; VEGFR 1

Indexed keywords

AMYLOID PRECURSOR PROTEIN; APH 1 PROTEIN, HUMAN; APH-1 PROTEIN, HUMAN; CADHERIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 4; MEMBRANE PROTEIN; NOTCH RECEPTOR; PRESENILIN 1; PRESENILIN 2; SECRETASE; SOMATOMEDIN C RECEPTOR; VASCULOTROPIN RECEPTOR 1;

ARTICLE; BIOLOGICAL MODEL; CELL MEMBRANE; CHEMISTRY; ENZYME SPECIFICITY; ENZYMOLOGY; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PHOSPHORYLATION; PROTEIN BINDING;

AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; CADHERINS; CELL MEMBRANE; MEMBRANE PROTEINS; MODELS, BIOLOGICAL; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHORYLATION; PRESENILIN-1; PRESENILIN-2; PROTEIN BINDING; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, IGF TYPE 1; RECEPTORS, NOTCH; SUBSTRATE SPECIFICITY; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1;

EID: 44249115334     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1582-4934.2008.00274.x     Document Type: Article

References (116)

1. Visconti RP, Richardson CD, Sato TN. Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci USA. 2002 99 : 8219 24.
2. Folkman J. Angiogenesis. Annu Rev Med. 2006 57 : 1 18.
3. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999 85 : 221 8.
4. Grant MB, May W, Caballero S, Brown G, Guthrie S, Mames R, Byrne B, Vaught T, Spoerri P, Peck A, Scott E. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med. 2002 8 : 607 12.
5. Schatteman GC. Adult bone marrow-derived heman-gioblasts, endothelial cell progenitors, and EPCs. Curr Top Dev Biol. 2004 64 : 141 80.
6. Cai J, Boulton M. The pathogenesis of diabetic retinopathy: old concepts and new questions. Eye. 2002 16 : 242 60.
7. Schlingemann RO. Role of growth factors and the wound healing response in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2004 242 : 91 101.
8. Tong JP, Yao YF. Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions. Clin Biochem. 2006 39 : 267 76.
9. Grant MB, Afzal A, Spoerri P, Pan H, Shaw LC, Mames RN. The role of growth factors in the patho-genesis of diabetic retinopathy. Expert Opin Investig Drugs. 2004 13 : 1275 93.
10. Borgstrom P, Gold DP, Hillan KJ, Ferrara N. Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res. 1999 19 : 4203 14.
11. van Wijngaarden P, Coster DJ, Williams KA. Inhibitors of ocular neovascularization: promises and potential problems. JAMA. 2005 293 : 1509 13.
12. Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 2003 22 : 1 29.
13. Choueiri TK, Bukowski RM, Rini BI. The current role of angiogenesis inhibitors in the treatment of renal cell carcinoma. Semin Oncol. 2006 33 : 596 606.
14. Rini BI. Vascular endothelial growth factor-targeted therapy in renal cell carcinoma: current status and future directions. Clin Cancer Res. 2007 13 : 1098 106.
15. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 355 : 1419 31.
16. Chang KH, Chang-Ling T, McFarland E, Afzal A, Pan H, Baxter L, Shaw L, Caballero S, Sengupta N, Li Calzi S, Sullivan S, Grant MB. IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development. Proc Natl Acad Sci USA. 2007 104 : 10595 600.
17. Zwick E, Bange J, Ullrich A. Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer. 2001 8 : 161 73.
18. Blazquez C, Cook N, Micklem K, Harris AL, Gatter KC, Pezzella F. Phosphorylated KDR can be located in the nucleus of neoplastic cells. Cell Res. 2006 16 : 93 8.
19. Carpenter G. Nuclear localization and possible functions of receptor tyrosine kinases. Curr Opin Cell Biol. 2003 15 : 143 8.
20. Fortini ME. Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling. Nat Rev Mol Cell Biol. 2002 3 : 673 84.
21. Heldin CH, Ericsson J. Signal transduction. RIPping tyrosine kinase receptors apart. Science. 2001 294 : 2111 3.
22. Landman N, Kim TW. Got RIP? Presenilin-dependent intramembrane proteolysis in growth factor receptor signaling. Cytokine Growth Factor Rev. 2004 15 : 337 51.
23. Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature. 1998 393 : 382 6.
24. Weihofen A, Binns K, Lemberg MK, Ashman K, Martoglio B. Identification of signal peptide pepti-dase, a presenilin-type aspartic protease. Science. 2002 296 : 2215 8.
25. Xia W, Wolfe MS. Intramembrane proteolysis by pre-senilin and presenilin-like proteases. J Cell Sci. 2003 116 : 2839 44.
26. Rawson RB. Regulated intramembrane proteolysis: from the endoplasmic reticulum to the nucleus. Essays Biochem. 2002 38 : 155 68.
27. Freeman M. Rhomboids. Curr Biol. 2003 13 : R586.
28. Moninka, N, Afzal A, Cai J, Chang K, Shaw L, Grant M, Boulton M. Cleavage and intracellular translocation of the-stromal derived factor -1 (sdf-1) receptor, CXCR4, regulates endothelial cell function. Invest Ophthalmol Vis Sci. 2008 48 : ARVO E-Abstract 1724.
29. Brunkan AL, Goate AM. Presenilin function and gamma-secretase activity. J Neurochem. 2005 93 : 769 92.
30. Wolfe MS. The gamma-secretase complex: membrane-embedded proteolytic ensemble. Biochemistry. 2006 45 : 7931 9.
31. Cai J, Jiang WG, Grant MB, Boulton M. Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor 1. J Biol Chem. 2006 281 : 3604 13.
32. De Strooper B. Nicastrin: gatekeeper of the gamma-secretase complex. Cell. 2005 122 : 318 20.
33. Shah S, Lee S, Tabuchi K, Hao Y, Yu C, LaPlant Q, Ball H, Dann C, Sudhof T, Yu G. Nicastrin functions as a gamma-secretase-substrate receptor. Cell. 2005 122 : 435 47.
34. Mastrangelo P, Matthews P, Chishti M, Schmidt S, Guy Y, Yang J, Mazella M, Coomaraswamy J, Horne P, Strome B, Pelly H, Levesque G, Ebeling C, Jiang Y, Nixon R, Rozmahel R, Fraser P, George-Hyslop P, Carlson G, Westaway D. Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases. Proc Natl Acad Sci USA. 2005 102 : 8972 7.
35. Kim SK, Park HJ, Hong HS, Baik EJ, Jung MW, Mook-Jung I. ERK1-2 is an endogenous negative regulator of the gamma-secretase activity. FASEB J. 2006 20 : 157 9.
36. Pastorcic M, Das HK. Alternative initiation of transcription of the human presenilin 1 gene in SH-SY5Y and SK-N-SH cells. The role of Ets factors in the regulation of presenilin 1. Eur J Biochem. 2004 271 : 4485 94.
37. Wang R, Zhang Y, Sun P, Liu R, Zhang X, Xia K, Xia J, Xu H, Zhang Z. Transcriptional regulation of PEN-2, a key component of the gamma-secretase complex, by CREB. Mol Cell Biol. 2006 26 : 1347 54.
38. Massey LK, Mah AL, Monteiro MJ. Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase components, Pen-2 and nicastrin. Biochem J. 2005 391 : 513 25.
39. Allinson TM, Parkin ET, Turner AJ, Hooper NM. ADAMs family members as amyloid precursor protein alpha-secretases. J Neurosci Res. 2003 74 : 342 52.
40. Brown MS, Ye J, Rawson RB, Goldstein JL. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell. 2000 100 : 391 8.
41. Koike H, Tomioka S, Sorimachi H, Saido T, Maruyama K, Okuyama A, Fujisawa-Sehara A, Ohno S, Suzuki K, Ishiura S. Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein. Biochem J. 1999 343 : 371 5.
42. Ni CY, Murphy MP, Golde TE, Carpenter G. gamma-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 2001 294 : 2179 81.
43. Selkoe D, Kopan R. Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration. Annu Rev Neurosci. 2003 26 : 565 97.
44. Kanning KC, Hudson M, Amieux PS, Wiley JC, Bothwell M, Schecterson LC. Proteolytic processing of the p75 neurotrophin receptor and two homologs generates C-terminal fragments with signaling capability. J Neurosci. 2003 23 : 5425 36.
45. Marambaud P, Shoi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, Baki L, Wen P, Efthimiopoulos S, Shao Z, Wisniewski T, Robakis N. A presenilin-1-gamma-secretase cleavage releases the E-cad-herin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 2002 21 : 1948 56.
46. Parks AL, Curtis D. Presenilin diversifies its portfolio. Trends Genet. 2007 23 : 140 50.
47. Murakami D, Okamoto I, Nagano O, Kawano Y, Tomita T, Iwatsubo T, De Strooper B, Yumoto E, Saya H. Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44. Oncogene. 2003 22 : 1511 6.
48. Jung KM, Tan S, Landman N, Petrova K, Murray S, Lewis R, Kim PK, Kim DS, Ryu SH, Chao MV, kim Tw. Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor. J Biol Chem. 2003 278 : 42161 9.
49. May P, Reddy YK, Herz J. Proteolytic processing of low density lipoprotein receptor-related protein mediates regulated release of its intracellular domain. J Biol Chem. 2002 277 : 18736 43.
50. McElroy B, Powell JC, McCarthy JV. The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis. Biochem Biophys Res Commun. 2007 358 : 1136 41.
51. Marron M, Singh H, Tahir T, Kavumkal J, Kim H, Koh G, Brindle NP. Regulated proteolytic processing of Tie1 modulates ligand responsiveness of receptor -tyrosine kinase Tie 2. J Biol Chem. 2007 282 : 30509 17.
52. Mukherjee S, Tessema M, Wandinger-Ness A. Vesicular trafficking of tyrosine kinase receptors and associated proteins in the regulation of signaling and vascular function. Circ Res. 2006 98 : 743 56.
53. Myers JM, Martins GG, Ostrowski J, Stachowiak MK. Nuclear trafficking of FGFR1: a role for the transmembrane domain. J Cell Biochem. 2003 88 : 1273 91.
54. Peng H, Moffett J, Myers J, Fang X, Stachowiak E, Maher P, Kratz E, Hines J, Fluharty S, Mizukoshi E, Bloom D, Stachowiak M. Novel nuclear signaling pathway mediates activation of fibroblast growth factor-2 gene by type 1 and type 2 angiotensin II receptors. Mol Biol Cell. 2001 12 : 449 62.
55. Reilly JF, Maher PA. Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation. J Cell Biol. 2001 152 : 1307 12.
56. Bild AH, Turkson J, Jove R. Cytoplasmic transport of Stat3 by receptor-mediated endocytosis. EMBO J. 2002 21 : 3255 63.
57. Suga K, Saito A, Tomiyama T, Mori H, Akagawa K. Syntaxin 5 interacts specifically with presenilin holo-proteins and affects processing of betaAPP in neuronal cells. J Neurochem. 2005 94 : 425 39.
58. McCarthy JV. Involvement of presenilins in cell-survival signalling pathways. Biochem Soc Trans. 2005 33 : 568 72.
59. Thomas AV, Herl L, Spoelgen R, Hiltunen M, Jones PB, Tanzi RE, Hyman BT, Berezovska O. Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader. J Biol Chem. 2006 281 : 26400 7.
60. Jo DG, Jang J, Kim BJ, Lundkvist J, Jung YK. Overexpression of calsenilin enhances gamma-secre-tase activity. Neurosci Lett. 2005 378 : 59 64.
61. Prat MI, Adamo A, Gonzalez S, Affranchino J, Ikeda M, Matsubara E, Shoji M, Smith M, Castano E, Morelli L. Presenilin 1 overexpressions in Chinese hamster ovary (CHO) cells decreases the phosphorylation of retinoblastoma protein: relevance for neurodegeneration. Neurosci Lett. 2002 326 : 9 12.
62. Georgakopoulos A, Litterst C, Ghersi E, Baki L, Xu C, Serban G, Robakis NK. Metalloproteinase/-Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling. EMBO J. 2006 25 : 1242 52.
63. Arasada RR, Carpenter G. Secretase-dependent tyrosine phosphorylation of Mdm2 by the ErbB-4 intracellular domain fragment. J Biol Chem. 2005 280 : 30783 7.
64. Maatta JA, Sundvall M, Junttila TT, Peri L, Laine VJ, Isola J, Egeblad M, Elenius K. Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4 isoform promote ligand-independent survival and cancer cell growth. Mol Biol Cell. 2006 17 : 67 79.
65. Baki L, Shioi J, Wen P, Shao Z, Schwarzman A, Gama-Sosa M, Neve R, Robakis NK. PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J. 2004 23 : 2586 96.
66. Kang DE, Yoon IS, Repetto E, Busse T, Yermian N, Ie L, Koo EH. Presenilins mediate phosphatidylinosi-tol 3-kinase-AKT and ERK activation via select signaling receptors. Selectivity of PS2 in platelet-derived growth factor signaling. J Biol Chem. 2005 280 : 31537 47.
67. Lukiw WJ, Gordon WC, Rogaev EI, Thompson H, Bazan NG. Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis. Neuroreport. 2001 12 : 53 7.
68. Nakajima M, Yuasa S, Ueno M, Takakura N, Koseki H, Shirasawa T. Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev. 2003 120 : 657 67.
69. Sainson RC, Aoto J, Nakatsu MN, Holderfield M, Conn E, Koller E, Hughes CC. Cell-autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis. FASEB J. 2005 19 : 1027 9.
70. Serneels L, Dejaegere T, Craessaerts K, Horre K, Jorissen E, Tousseyn T, Hebert S, Coolen M, Martens G, Zwijsen A, Annaert W, Hartmann D, De Strooper B. Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo. Proc Natl Acad Sci USA. 2005 102 : 1719 24.
71. Shi W, Harris AL. Notch signaling in breast cancer and tumor angiogenesis: cross-talk and therapeutic potentials. J Mammary Gland Biol Neoplasia. 2006 11 : 41 52.
72. Williams CK, Li JL, Murga M, Harris AL, Tosato G. Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood. 2006 107 : 931 9.
73. Nakajima M, Ogawa M, Shimoda Y, Hiraoka S, Iida M, Koseki H, Shirasawa T, Furukawa K. Presenilin-1 controls the growth and differentiation of endothelial progenitor cells through its beta-catenin-binding region. Cell Biol Int. 2006 30 : 239 43.
74. Murakami Y, Yamagoe S, Noguchi K, Takebe Y, Takahashi N, Uehara Y, Fukazawa H. Ets-1-dependent expression of vascular endothelial growth factor receptors is activated by latency-associated nuclear antigen of Kaposi's sarcoma-associated herpes virus through Interaction with Daxx. J Biol Chem. 2006 281 : 28113 21.
75. Mayo LD, Kessler KM, Pincheira R, Warren RS, Donner DB. Vascular endothelial cell growth factor activates CRE-binding protein by signaling through the KDR receptor tyrosine kinase. J Biol Chem. 2001 276 : 25184 9.
76. Curry CL, Reed LL, Nickoloff BJ, Miele L, Foreman KE. Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells. Lab Invest. 2006 86 : 842 52.
77. Taylor KL, Henderson AM, Hughes CC. Notch activation during endothelial cell network formation in vitro targets the basic HLH transcription factor HESR-1 and downregulates VEGFR-2-KDR expression. Microvasc Res. 2002 64 : 372 83.
78. Takeshita K, Satoh M, Li M, Silver M, Limbourg F, Mukai Y, Rikitake Y, Radtke F, Gridley T, Losordo D, Liao J. Critical role of endothelial Notch1 signaling in postnatal angiogenesis. Circ Res. 2007 100 : 70 8.
79. Liu ZJ, Shirakawa T, Li Y, Soma A, Oka M, Dotto GP, Fairman RM, Velazquez OC, Herlyn M. Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Mol Cell Biol. 2003 23 : 14 25.
80. Wang Z, Banerjee S, Li Y, Rahman KM, Zhang Y, Sarkar FH. Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res. 2006 66 : 2778 84.
81. Hellstrom M, Phng L, Hofmann J, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson A, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe M, Kalem M, Gerhardt H, Betsholtz C. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007 445 : 776 80.
82. Hainaud P, Contreres JO, Villemain A, Liu LX, Plouet J, Tobelem G, Dupuy E. The role of the vascular endothelial growth factor-Delta-like 4 ligand-Notch4-ephrin B2 cascade in tumor vessel remodeling and endothelial cell functions. Cancer Res. 2006 66 : 8501 10.
83. Harrington LS, Sainson RC, Williams CK, Taylor JM, Shi W, Li JL, Harris AL. Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells. Microvasc Res. 2008 75 : 144 54.
84. Thurston G, Noguera-Troise I, Yancopoulos GD. The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat Rev Cancer. 2007 7 : 327 31.
85. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA. 1998 95 : 9349 54.
86. Nozaki M, Sakurai E, Raisler B, Baffi J, Witta J, Ogura Y, Brekken R, Sage E, Ambati B, Ambati J. Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A. J Clin Invest. 2006 116 : 422 9.
87. Yen L, Benlimame N, Nie Z, Xiao D, Wang T, Al Moustafa E, Esumi H, Milanini J, Hynes N, Pages G, Alaoui-Jamali. Differential regulation of tumor angiogenesis by distinct ErbB homo- and heterodimers. Mol Biol Cell. 2002 13 : 4029 44.
88. Omerovic J, Puggioni EM, Napoletano S, Visco V, Fraioli R, Frati L, Gulino A, Alimandi M. Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level. Exp Cell Res. 2004 294 : 469 79.
89. Ni CY, Yuan H, Carpenter G. Role of the ErbB-4 car-boxyl terminus in gamma-secretase cleavage. J Biol Chem. 2003 278 : 4561 5.
90. Zhang YW, Wang R, Liu Q, Zhang H, Liao FF, Xu H. Presenilin-gamma- secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression. Proc Natl Acad Sci USA. 2007 104 : 10613 8.
91. Amin DN, Hida K, Bielenberg DR, Klagsbrun M. Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors. Cancer Res. 2006 66 : 2173 80.
92. Bueter W, Dammann O, Zscheppang K, Korenbaum E, Dammann CE. ErbB receptors in fetal endothelium-a potential linkage point for inflammation-associated neonatal disorders. Cytokine. 2006 36 : 267 75.
93. Kim HS, Shin HS, Kwak HJ, Cho CH, Lee CO, Koh GY. Betacellulin induces angiogenesis through activation of mitogen-activated protein kinase and phosphatidylinositol 3′-kinase in endothelial cell. FASEB J. 2003 17 : 318 20.
94. Nakano N, Higashiyama S, Ohmoto H, Ishiguro H, Taniguchi N, Wada Y. The N-terminal region of NTAK-neuregulin-2 isoforms has an inhibitory activity on angiogenesis. J Biol Chem. 2004 279 : 11465 70.
95. Russell KS, Stern DF, Polverini PJ, Bender JR. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol. 1999 277 : H2205 11.
96. Xiong S, Grijalva R, Zhang L, Nguyen NT, Pisters PW, Pollock RE, Yu D. Up-regulation of vascular endothelial growth factor in breast cancer cells by the heregulin-beta1-activated p38 signaling pathway enhances endothelial cell migration. Cancer Res. 2001 61 : 1727 32.
97. Gulino D, Delachanal E, Concord E, Genoux Y, Morand B, Valiron M, Sulpice E, Scaife R, Alemany M, Vernet T. Alteration of endothelial cell monolayer integrity triggers resynthesis of vascular endothelium cadherin. J Biol Chem. 1998 273 : 29786 93.
98. Navarro P, Caveda L, Breviario F, Mandoteanu I, Lampugnani MG, Dejana E. Catenin-dependent and -independent functions of vascular endothelial cadherin. J Biol Chem. 1995 270 : 30965 72.
99. Prandini MH, Dreher I, Bouillot S, Benkerri S, Moll T, Huber P. The human VE-cadherin promoter is subjected to organ-specific regulation and is activated in tumour angiogenesis. Oncogene. 2005 24 : 2992 3001.
100. Parisiadou L, Fassa A, Fotinopoulou A, Bethani I, Efthimiopoulos S. Presenilin 1 and cadherins: stabilization of cell-cell adhesion and proteolysis-dependent regulation of transcription. Neurodegener Dis. 2004 1 : 184 91.
101. Georgakopoulos A, Marambaud P, Friedrich VL Jr., Shioi J, Efthimiopoulos S, Robakis NK. Presenilin-1: a component of synaptic and endothelial adherens junctions. Ann N Y Acad Sci. 2000 920 : 209 14.
102. Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res. 2001 20 : 705 32.
103. Yoshida T, Ohno-Matsui K, Ichinose S, Sato T, Iwata N, Saido TC, Hisatomi T, Mochizuki M, Morita I. The potential role of amyloid beta in the pathogenesis of age-related macular degeneration. J Clin Invest. 2005 115 : 2793 800.
104. Zhang Y, Cai J, Afzal A, Grant M, Boulton M. VEGFR-1 is differentially regulated by pigment epithelium-derived factor (PEDF) via presenilin in RPE and retinal endothelial cells. Invest Ophthalmol Vis Sci. 2006 47 : ARVO E-Abstract 5333.
105. Yoneda S, Hara H, Hirata A, Fukushima M, Inomata Y, Tanihara H. Vitreous fluid levels of beta-amyloid((1-42)) and tau in patients with retinal diseases. Jpn J Ophthalmol. 2005 49 : 106 8.
106. Hara H, Oh-hashi K, Yoneda S, Shimazawa M, Inatani M, Tanihara H, Kiuchi K. Elevated neprilysin activity in vitreous of patients with proliferative diabetic retinopathy. Mol Vis. 2006 12 : 977 82.
107. Lazarov O, Robinson J, Tang Y, Hairston I, Korade-Mimics Z, Lee V, Hersh L, Sapolsky R, Mimics K, Sisodia S. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell. 2005 120 : 701 13.
108. Cowan JW, Wang X, Guan R, He K, Jiang J, Baumann G, Black RA, Wolfe MS, Frank SJ. Growth hormone receptor is a target for presenilin-dependent gamma-secretase cleavage. J Biol Chem. 2005 280 : 19331 42.
109. Schulz JG, Annaert W, Vandekerckhove J, Zimmermann P, De Strooper B, David G. Syndecan 3 intramembrane proteolysis is presenilin-gamma-secretase- dependent and modulates cytosolic signaling. J Biol Chem. 2003 278 : 48651 7.
110. Wang R, Tang P, Wang P, Boissy RE, Zheng H. Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation. Proc Natl Acad Sci USA. 2006 103 : 353 8.
111. Cui W, Ke JZ, Zhang Q, Ke HZ, Chalouni C, Vignery A. The intracellular domain of CD44 promotes the fusion of macrophages. Blood. 2006 107 : 796 805.
112. Carey BW, Kim DY, Kovacs DM. Presenilin-gamma-secretase and alpha-secretase-like peptidases cleave human MHC Class I proteins. Biochem J. 2007 401 : 121 7.
113. Evin G, Sernee MF, Masters CL. Inhibition of gamma-secretase as a therapeutic intervention for Alzheimer's disease: prospects, limitations and strategies. CNS Drugs. 2006 20 : 351 72.
114. Milano J, Mckay J, Dagenais C, Foster-Brown L, Pognan F, Gadient R, Jacobs R, Zacco A, Greenberg B, Ciaccio P. Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol Sci. 2004 82 : 341 58.
115. Ni Y, Xhao X, Bao G, Zou L, Teng L, Wang Z, Song M, Xiong J, Bai Y, Pei G. Activation of beta2-adrener-gic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med. 2006 12 : 1390 6.
116. Czech C, Burns MP, Vardanian L, Augustin A, Jacobsen H, Baumann K, Rebeck GW. Cholesterol independent effect of LXR agonist TO-901317 on gamma-secretase. J Neurochem. 2007 101 : 929 36.