Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation

Journal of Clinical Investigation

Volumn 126, Issue 9, 2016, Pages 3511-3525

  Kim, Minah ^a   Allen, Breanna ^a   Korhonen, Emilia A ^b   Nitschké, Maximilian ^a   Yang, Hee Won ^c   Baluk, Peter ^a   Saharinen, Pipsa ^b   Alitalo, Kari ^b   Daly, Christopher ^d   Thurston, Gavin ^d   McDonald, Donald M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF HELSINKI   (Finland)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d REGENERON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN 2; ANGIOPOIETIN RECEPTOR; HUMAN MONOCLONAL ANTIBODY; IMMUNOGLOBULIN G; NESVACUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; REGN 1376; TRANSCRIPTION FACTOR FKHR; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR; FOXO1 PROTEIN, MOUSE; MONOCLONAL ANTIBODY; VASCULOTROPIN A;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; FEMALE; GENE ACTIVATION; GENE INACTIVATION; GENE OVEREXPRESSION; IN VIVO STUDY; MALE; MOUSE; MYCOPLASMA PULMONIS; MYCOPLASMOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; SIGNAL TRANSDUCTION; VASCULAR REMODELING; VASCULARIZATION; ANIMAL; ANTAGONISTS AND INHIBITORS; C3H MOUSE; C57BL MOUSE; CHEMISTRY; ENDOTHELIUM CELL; HUMAN; INFLAMMATION; METABOLISM; PROTEIN DOMAIN; TRANSGENIC MOUSE; VASCULAR ENDOTHELIUM;

ANGIOPOIETIN-2; ANIMALS; ANTIBODIES, MONOCLONAL; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; FEMALE; FORKHEAD BOX PROTEIN O1; HUMANS; INFLAMMATION; MALE; MICE; MICE, INBRED C3H; MICE, INBRED C57BL; MICE, TRANSGENIC; MYCOPLASMA PULMONIS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN DOMAINS; RECEPTOR, TIE-2; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR REMODELING;

EID: 84987806983     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI84871     Document Type: Article

References (77)

1. Augustin HG, Koh GY, Thurston G, Alitalo K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol. 2009;10(3):165-177
2. Baluk P, et al. TNF-alpha drives remodeling of blood vessels and lymphatics in sustained airway inflammation in mice. J Clin Invest. 2009;119(10):2954-2964
3. Lee CG, et al. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med. 2004;10(10):1095-1103
4. Tabruyn SP, et al. Angiopoietin-2-driven vascular remodeling in airway inflammation. Am J Pathol. 2010;177(6):3233-3243
5. Sato TN, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature. 1995;376(6535):70-74
6. Suri C, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996;87(7):1171-1180
7. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407(6801):242-248
8. Puri MC, Rossant J, Alitalo K, Bernstein A, Partanen J. The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBO J. 1995;14(23):5884-5891
9. Saharinen P, et al. Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol. 2008;10(5):527-537
10. Brunet A, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96(6):857-868
11. Daly C, et al. Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1). Genes Dev. 2004;18(9):1060-1071
12. Kim I, Kim HG, So JN, Kim JH, Kwak HJ, Koh GY. Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/ Akt signal transduction pathway. Circ Res. 2000;86(1):24-29
13. Potente M, et al. Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Invest. 2005;115(9):2382-2392
14. Zhang X, et al. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. J Biol Chem. 2002;277(47):45276-45284
15. Maisonpierre PC, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277(5322):55-60
16. Benest AV, et al. Angiopoietin-2 is critical for cytokine-induced vascular leakage. PLoS ONE. 2013;8(8):e70459
17. Le CT, et al. Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-α in suppressing remodeling of blood vessels and lymphatics in airway inflammation. Am J Pathol. 2015;185(11):2949-2968
18. Parikh SM, et al. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med. 2006;3(3):e46
19. Ziegler T, et al. Angiopoietin 2 mediates microvascular hemodynamic alterations in sepsis. J Clin Invest. 2013;123(8):3436-3445
20. Daly C, et al. Angiopoietin-2 functions as an autocrine protective factor in stressed endothelial cells. Proc Natl Acad Sci U S A. 2006;103(42):15491-15496
21. Davis S, et al. Angiopoietins have distinct modular domains essential for receptor binding, dimerization and superclustering. Nat Struct Biol. 2003;10(1):38-44
22. Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG. The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci. 2005;118(Pt 4):771-780
23. Yuan HT, Khankin EV, Karumanchi SA, Parikh SM. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol. 2009;29(8):2011-2022
24. Daly C, et al. Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the effects of VEGF inhibition. Cancer Res. 2013;73(1):108-118
25. Hammes HP, et al. Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy. Diabetes. 2004;53(4):1104-1110
26. Holash J, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284(5422):1994-1998
27. Fiedler U, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12(2):235-239
28. Fiedler U, et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. 2004;103(11):4150-4156
29. Singh H, Hansen TM, Patel N, Brindle NP. The molecular balance between receptor tyrosine kinases Tie1 and Tie2 is dynamically controlled by VEGF and TNFα and regulates angiopoietin signalling. PLoS ONE. 2012;7(1):e29319
30. Bureau W, et al. Chronic systemic delivery of angiopoietin-2 reveals a possible independent angiogenic effect. Am J Physiol Heart Circ Physiol. 2006;291(2):H948-H956
31. Kim KE, Cho CH, Kim HZ, Baluk P, McDonald DM, Koh GY. In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic vessels in mouse airways and skin. Arterioscler Thromb Vasc Biol. 2007;27(3):564-570
32. Thurston G, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science. 1999;286(5449):2511-2514
33. Boscolo E, et al. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest. 2015;125(9):3491-3504
34. Vikkula M, et al. Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell. 1996;87(7):1181-1190
35. Fuxe J, et al. Angiopoietin/Tie2 signaling transforms capillaries into venules primed for leukocyte trafficking in airway inflammation. Am J Pathol. 2010;176(4):2009-2018
36. Fuxe J, et al. Pericyte requirement for anti-leak action of angiopoietin-1 and vascular remodeling in sustained inflammation. Am J Pathol. 2011;178(6):2897-2909
37. Thurston G, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 2000;6(4):460-463
38. Korhonen EA, et al. Tie1 controls angiopoietin function in vascular remodeling and inflammation. J Clin Invest. 2016;126(9):3495-3510
39. Sarao R, Dumont DJ. Conditional transgene expression in endothelial cells. Transgenic Res. 1998;7(6):421-427
40. Baluk P, et al. Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways. Am J Pathol. 2004;165(4):1071-1085
41. Thurston G, Murphy TJ, Baluk P, Lindsey JR, McDonald DM. Angiogenesis in mice with chronic airway inflammation: strain-dependent differences. Am J Pathol. 1998;153(4):1099-1112
42. Ezaki T, Baluk P, Thurston G, La Barbara A, Woo C, McDonald DM. Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation. Am J Pathol. 2001;158(6):2043-2055
43. Gong S, et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature. 2003;425(6961):917-925
44. Cartner SC, Simecka JW, Lindsey JR, Cassell GH, Davis JK. Chronic respiratory mycoplasmosis in C3H/HeN and C57BL/6N mice: lesion severity and antibody response. Infect Immun. 1995;63(10):4138-4142
45. Wong AL, Haroon ZA, Werner S, Dewhirst MW, Greenberg CS, Peters KG. Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues. Circ Res. 1997;81(4):567-574
46. Jones N, et al. Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. J Biol Chem. 1999;274(43):30896-30905
47. Kontos CD, et al. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol. 1998;18(7):4131-4140
48. Suri C, et al. Increased vascularization in mice overexpressing angiopoietin-1. Science. 1998;282(5388):468-471
49. Baffert F, Thurston G, Rochon-Duck M, Le T, Brekken R, McDonald DM. Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1-induced plasticity of adult blood vessels. Circ Res. 2004;94(7):984-992
50. Cho CH, et al. Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and enhanced blood flow. Circ Res. 2005;97(1):86-94
51. Hackett SF, Wiegand S, Yancopoulos G, Campochiaro PA. Angiopoietin-2 plays an important role in retinal angiogenesis. J Cell Physiol. 2002;192(2):182-187
52. Reiss Y, et al. Angiopoietin-2 impairs revascularization after limb ischemia. Circ Res. 2007;101(1):88-96
53. Yabkowitz R, Meyer S, Black T, Elliott G, Merewether LA, Yamane HK. Inflammatory cytokines and vascular endothelial growth factor stimulate the release of soluble tie receptor from human endothelial cells via metalloprotease activation. Blood. 1999;93(6):1969-1979
54. Cho CH, et al. COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity. Proc Natl Acad Sci U S A. 2004;101(15):5547-5552
55. McDonald DM. Endothelial gaps and permeability of venules in rat tracheas exposed to inflammatory stimuli. Am J Physiol. 1994;266(1 Pt 1):L61-L83
56. Gale NW, et al. Complementary and coordinated roles of the VEGFs and angiopoietins during normal and pathologic vascular formation. Cold Spring Harb Symp Quant Biol. 2002;67:267-273
57. Bogdanovic E, Nguyen VP, Dumont DJ. Activation of Tie2 by angiopoietin-1 and angiopoietin-2 results in their release and receptor internalization. J Cell Sci. 2006;119(Pt 17):3551-3560
58. Kim I, Kim JH, Moon SO, Kwak HJ, Kim NG, Koh GY. Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3'-kinase/ Akt signal transduction pathway. Oncogene. 2000;19(39):4549-4552
59. Teichert-Kuliszewska K, et al. Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res. 2001;49(3):659-670
60. Shen J, et al. Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature. J Clin Invest. 2014;124(10):4564-4576
61. Gale NW, et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 2002;3(3):411-423
62. Pitera JE, Woolf AS, Gale NW, Yancopoulos GD, Yuan HT. Dysmorphogenesis of kidney cortical peritubular capillaries in angiopoietin-2-deficient mice. Am J Pathol. 2004;165(6):1895-1906
63. Shimoda H, Bernas MJ, Witte MH, Gale NW, Yancopoulos GD, Kato S. Abnormal recruitment of periendothelial cells to lymphatic capillaries in digestive organs of angiopoietin-2-deficient mice. Cell Tissue Res. 2007;328(2):329-337
64. Dellinger M, et al. Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient mice. Dev Biol. 2008;319(2):309-320
65. Brown JL, et al. A human monoclonal anti-ANG2 antibody leads to broad antitumor activity in combination with VEGF inhibitors and chemotherapy agents in preclinical models. Mol Cancer Ther. 2010;9(1):145-156
66. Felcht M, et al. Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest. 2012;122(6):1991-2005
67. Hakanpaa L, et al. Endothelial destabilization by angiopoietin-2 via integrin β1 activation. Nat Commun. 2015;6:5962
68. Furuyama T, et al. Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice. J Biol Chem. 2004;279(33):34741-34749
69. Taddei A, et al. Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol. 2008;10(8):923-934
70. Choi HJ, et al. Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2. Nat Commun. 2015;6:6943
71. McClatchey AI, Yap AS. Contact inhibition (of proliferation) redux. Curr Opin Cell Biol. 2012;24(5):685-694
72. Papapetropoulos A, et al. Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. J Biol Chem. 2000;275(13):9102-9105
73. Kanda S, Miyata Y, Mochizuki Y, Matsuyama T, Kanetake H. Angiopoietin 1 is mitogenic for cultured endothelial cells. Cancer Res. 2005;65(15):6820-6827
74. Fukuhara S, et al. Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat Cell Biol. 2008;10(5):513-526
75. Lee J, et al. Angiopoietin-1 guides directional angiogenesis through integrin αvβ5 signaling for recovery of ischemic retinopathy. Sci Transl Med. 2013;5(203):203ra127
76. Adler AP, et al. Blockade of angiopoietin-2 or Tie2 is equally effective at inhibiting tumor growth and reducing tumor vessel density in most human tumor xenograft models [AACR abstract 4492]. Cancer Res. 2014;74(19 suppl)
77. Lonetti A, et al. Activity of the pan-class I phosphoinositide 3-kinase inhibitor NVP-BKM120 in T-cell acute lymphoblastic leukemia. Leukemia. 2014;28(6):1196-1206