Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway

Abstract

The angiopoietin-Tie2 system in endothelial cells is an important regulator of vasculogenesis and vascular integrity. High levels of angiopoietin-2 (Ang2) mRNA are observed in vascular activation during tumorigenesis. Although Ang2 is known to be a naturally occurring antagonist of angiopoietin-1 (Ang1) in vivo, the exact function of Ang2 itself is not known. Here, we found that a high concentration of Ang2 (800 ng/ml) acts as an apoptosis survival factor for endothelial cells during serum deprivation apoptosis. The survival effect of high concentration Ang2 was blocked by pre-treatment with soluble Tie2 receptor and the PI 3′-kinase-specific inhibitors, wortmannin and LY294002. Accordingly, 800 ng/ml of Ang2 induced phosphorylation of Tie2, the p85 subunit of phosphatidylinositol 3′-kinase (PI 3′-kinase), and serine-threonine kinase Akt at Ser473 in the human umbilical vein endothelial cells; lower concentrations of Ang2 (50–400 ng/ml) did not produce notable effects. These findings indicate that at high concentrations, Ang2, like Ang1, can be an apoptosis survival factor for endothelial cells through the activation of the Tie2 receptor, PI 3′-kinase and Akt, and thus may be a positive regulator of tumor angiogenesis.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, Yancopoulos GD and Isner JM. . 1998 Circ. Res. 83: 233–240.

  • Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, Frisch S and Reed JC. . 1998 Science 282: 1318–1321.

  • Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg MG. . 1997 Cell 91: 231–241.

  • Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC and Yancopoulos GD. . 1996 Cell 87: 1161–1169.

  • Dunk C, Shams M, Nijjar S, Rhaman M, Qiu Y, Bussolati B and Ahmed A. . 2000 Am. J. Pathol. 156: 2185–2199.

  • Hanahan D. . 1997 Science 277: 48–50.

  • Hanahan D and Folkman J. . (1996) Cell 86: 353–364.

  • Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD and Wiegand SJ. . 1999 Science 284: 1994–1998.

  • Kim I, Kim HG, So J-N, Kim JH, Kwak HJ and Koh GY. . 2000a Circ. Res. 86: 24–29.

  • Kim I, Kim J-H, Ryu YS, Jung SH, Nah JJ and Koh GY. . 2000b J. Biol. Chem. 275: 18550–18556.

  • Kim I, Moon S-O, Koh KN, Kim H, Uhm CS, Kwak HJ, Kim NG and Koh GY. . 1999 J. Biol. Chem. 274: 26523–26528.

  • Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U and Risau W. . 1998 Curr. Biol. 8: 529–532.

  • Kwak HJ, So J-N, Lee SJ, Kim I and Koh GY. . 1999 FEBS Lett. 448: 249–253.

  • Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN and Yancopoulos GD. . 1997 Science 277: 55–60.

  • Mandriota ST and Pepper MS. . 1998 Circ. Res. 83: 852–859.

  • Oh H, Takagi H, Suzuma K, Otani A, Matsumura M and Honda Y. . 1999 J. Biol. Chem. 274: 15732–15739.

  • Papapetropoulos A, Fulton D, Mahboubi K, Kalb RG, O'Connor DS, Li F, Altieri DC and Sessa WC. . 2000 J. Biol. Chem. 275: 9102–9105.

  • Papapetropoulos A, Garcia-Cardena G, Dengler TJ, Maisonpierre PC, Yancopoulos GD, and Sessa WC. . 1999 Lab. Invest. 79: 213–223.

  • Risau W. . 1995 FASEB J. 9: 926–933.

  • Risau W. . 1997 Nature 386: 671–674.

  • Shyu KG, Manor O, Magner M, Yancopoulos GD and Isner JM. . 1998 Circulation 98: 2081–2087.

  • Stratmann A, Risau W and Plate KH. . 1998 Am. J. Pathol. 153: 1459–1466.

  • Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN and Yancopoulos GD. . 1996 Cell 87: 1171–1180.

  • Suri C, McClain J, Thursyon G, McDonald DM, Zhou H, Oldmixon EH, Sato TN and Yancopoulos GD. . 1998 Science 282: 468–471.

  • Tanaka S, Mori M, Sakamoto Y, Makuuchi M, Sugimachi K and Wands JR. . 1999 J. Clin. Invest. 103: 341–345.

  • Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM and Yancopoulos GD. . 2000 Nat. Med. 6: 460–463.

  • Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD and McDonald DM. . 1999 Science 286: 2511–2514.

  • Witzenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD and Isner JM. . 1998 J. Biol. Chem. 273: 18514–18521.

Download references

Acknowledgements

This work was supported by the Creative Research Initiatives of the Korean Ministry of Science and Technology. We thank PC Maisonpierre and GD Yancopoulos for providing Ang2 and rTie2-Fc reagents. We thank J Macke for help in preparing the manuscript.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, I., Kim, JH., Moon, SO. et al. Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Oncogene 19, 4549–4552 (2000). https://doi.org/10.1038/sj.onc.1203800

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203800

Keywords

This article is cited by

Search

Quick links