Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation

Abstract

TIE-1 and Tie-2 define a new class of receptor tyrosine kinases that are specifically expressed in developing vascular endothelial cells. To study the functions of Tie-1 and Tie-2 during vascular endothelial cell growth and differentiation in vivo, targeted mutations of the genes in mice were introduced by homologous recombination. Embryos deficient in Tie-1 failed to establish structural integrity of vascular endothelial cells, resulting in oedema and subsequently localized haemorrhage. However, analyses of embryos deficient in Tie-2 showed that it is important in angiogen-esis, particularly for vascular network formation in endothelial cells. This result contrasts with previous reports on Tie-2 function in vasculogenesis and/or endothelial cell survival. Our in vivo analyses indicate that the structurally related receptor tyrosine kinases Tie-1 and Tie-2 have important but distinct roles in the formation of blood vessels.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Risau, W. in The Development of the Vascular System (eds Feinberg, R. N., Shere, G. K. & Auerbach, R.) 58–68 (Karger, Basel, 1991).

    Google Scholar 

  2. 2

    Risau, W. et al. Development 102, 471–478 (1988).

    CAS  PubMed  Google Scholar 

  3. 3

    Folkman, J. & Shing, Y. J. biol. Chem. 267, 10931–10934 (1992).

    CAS  Google Scholar 

  4. 4

    Folkman, J. Semin. Cancer Biol. 3, 65–71 (1992).

    CAS  PubMed  Google Scholar 

  5. 5

    De Vries, C. et al. Science 255, 989–991 (1992).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Dumont, D. J., Gradwohl, G. J., Fong, G.-H., Auerbach, R. & Breitman, M. L. Oncogene 8, 1293–1301 (1993).

    CAS  PubMed  Google Scholar 

  7. 7

    Iwama, A. et al. Biochem. biophys. Res. Commun. 195, 301–309 (1993).

    CAS  Article  Google Scholar 

  8. 8

    Maisonpierre, P. C., Goldfarb, M., Yancopoulos, G. D. & Gao, G. Oncogene 8, 1631–1637 (1993).

    CAS  PubMed  Google Scholar 

  9. 9

    Matthews, W. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9026–9030 (1991).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Millauer, B. et al. Cell 72, 835–846 (1993).

    CAS  Article  Google Scholar 

  11. 11

    Oelrichs, R. B., Reid, H. H., Bernard, O., Ziemiecki, A. & Wilks, A. F. Oncogene 8, 11–18 (1993).

    CAS  PubMed  Google Scholar 

  12. 12

    Partanen, J. et al. Molec. cell. Biol. 12, 1698–1707 (1992).

    CAS  Article  Google Scholar 

  13. 13

    Quinn, T. P., Peters, K. G., De, V. C., Ferrara, N. & Williams, L. T. Proc. natn. Acad. Sci. U.S.A. 90, 7533–7537 (1993).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Schnurch, H. & Risau, W. Development 119, 957–968 (1993).

    CAS  PubMed  Google Scholar 

  15. 15

    Sato, T. N., Qin, Y., Kozak, C. A. & Audus, K. L. Proc. natn. Acad. Sci. U.S.A. 90, 9355–9358 (1993).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Terman, B. J. et al. Biochem. biophys. Res. Commun. 187, 1579–1586 (1992).

    CAS  Article  Google Scholar 

  17. 17

    Yamaguchi, T. P., Dumont, D. J., Conlon, R. A., Brietman, M. L. & Rossant J. Development 118, 489–498 (1993).

    CAS  PubMed  Google Scholar 

  18. 18

    Ziegler, S. F., Bird, T. A., Schneringer, K. A., Schooley, K. A. & Baum, P. R. Oncogene 8, 663–670 (1993).

    CAS  PubMed  Google Scholar 

  19. 19

    Dumont, D. J. et al. Genes Dev. 8, 1897–1909 (1994).

    CAS  Article  Google Scholar 

  20. 20

    Kastner, P. et al. Cell 78, 987–1003 (1994).

    CAS  Article  Google Scholar 

  21. 21

    Sucov, H. M. et al. Genes Dev. 8, 1007–1018 (1994).

    CAS  Article  Google Scholar 

  22. 22

    Vecchi, A. et al. Eur. J. Cell Biol. 63, 247–254 (1994).

    CAS  PubMed  Google Scholar 

  23. 23

    Viragh, S. & Challice, C. E. Anat. Rec. 201, 157–168 (1981).

    CAS  Article  Google Scholar 

  24. 24

    Wagner, E. F. & Risau, W. Semin. Cancer Biol. 5, 137–145 (1994).

    CAS  PubMed  Google Scholar 

  25. 25

    Schlaeger, T. M., Qin, Y., Fujiwara, Y., Magram, J. & Sato, T. N. Development 121, 1089–1098 (1995).

    CAS  PubMed  Google Scholar 

  26. 26

    Kaipainen, A. et al. Cancer Res. 54, 6571–6577 (1994).

    CAS  PubMed  Google Scholar 

  27. 27

    Plate, K., Breier, G., Weich, H. A. & Risau, W. Nature 359, 845–848 (1992).

    ADS  CAS  Article  Google Scholar 

  28. 28

    Plate, K., Breier, G., Weich, H. A., Mennel, H. D. & Risau, W. Int. J. Cancer 59, 520–529 (1994).

    CAS  Article  Google Scholar 

  29. 29

    Swiatek, P. J. & Gridley, T. Genes Dev. 7, 2071–2084 (1993).

    CAS  Article  Google Scholar 

  30. 30

    Qin, Y. & Sato, T. N. Dev. Dynam. 202, 172–180 (1995).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sato, T., Tozawa, Y., Deutsch, U. et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376, 70–74 (1995). https://doi.org/10.1038/376070a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing