Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor

Article metrics

Abstract

THE peptide angiotensin II is the effector molecule of the renin-angiotensin system. All the haemodynamic effects of angiotensin II, including vasoconstriction and adrenal aldosterone release, are mediated through a single class of cell-surface receptors known as AT1 (refs 1, 2). These receptors contain the structural features of the G-protein-coupled receptor superfamily3. We show here that angiotensin II induces the rapid phosphorylation of tyrosine in the intracellular kinases Jak2 and Tyk2 in rat aortic smooth-muscle cells and that this phosphorylation is associated with increased activity of Jak2. The Jak family substrates STAT1 and STAT2 (for signal transducers and activators of transcription) are rapidly tyrosine-phosphorylated in response to angiotensin II. We also find that Jak2 co-precipitates with the AT1, receptor, indicating that G-protein-coupled receptors may be able to signal through the intracellular phosphorylation pathways used by cytokine receptors4,5.

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

    Peach, M. J. Physiol. Rev. 57, 313–337 (1977).

  2. 2

    Peach, M. J. Biochem. Pharmac. 30, 2745–2751 (1981).

  3. 3

    Murphy, T. J., Alexander, R. W., Griendling, K. K., Runge, M. S. & Bernstein, K. E. Nature 351, 233–236 (1991).

  4. 4

    Watling, D. et al. Nature 366, 166–170 (1993).

  5. 5

    Silvennoinen, O., Ihle, J. N., Schlessinger, J. & Levy, D. E. Nature 366, 583–585 (1993).

  6. 6

    Shuai, K. et al. Nature 366, 580–583 (1993).

  7. 7

    Velazquez, L., Fellous, M., Stark, G. R. & Pellegrini, S. Cell 70, 313–322 (1992).

  8. 8

    Rui, H., Kirken, R. & Farrar, W. L. J. biol. Chem. 269, 5364–5368 (1994).

  9. 9

    Bhat, G. J., Thekkumkara, T. J., Thomas, W. G., Conrad, K. M. & Baker, K. M. J. biol. Chem. 269, 31443–31449 (1994).

  10. 10

    Cohen, P. Nature 296, 613–617 (1982).

  11. 11

    Pazin, M. J. & Williams, L. T. Trends biochem Sci. 17, 374–378 (1992).

  12. 12

    Fantl, W. & Williams, L. T. A. Rev. Biochem. 62, 453–481 (1993).

  13. 13

    Schlessinger, J. & Ullrich, A. Neuron 9, 383–391 (1992).

  14. 14

    Cadena, D. L. & Gill, G. N. FASEB J. 6, 2332–2337 (1992).

  15. 15

    Silvennoinen, O. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8429–8433 (1993).

  16. 16

    Miura, O. et al. Blood 84, 1501–1507 (1994).

  17. 17

    Keegan, A. D. et al. Cell 76, 811–820 (1994).

  18. 18

    Savarese, T. M. & Fraser, C. M. Biochem. J. 283, 1–19 (1992).

  19. 19

    Dohlman, H. G., Thorner, J., Caron, M. G. & Lefkowitz, R. J. A. Rev. Biochem. 60, 651–688 (1992).

  20. 20

    Marrero, M. B., Paxton, W. G., Duff, J. L., Berk, B. C. & Bernstein, K. E. J. biol. Chem. 269, 10935–10939 (1994).

  21. 21

    Schorb, W., Peeler, T. C., Madigan, N. M., Conrad, K. M. & Baker, K. M. J. biol. Chem. 269, 19626–19632 (1994).

  22. 22

    Geisterfer, A. A. T., Peach, M. J. & Owens, G. K. Circ. Res. 62, 749–756 (1988).

  23. 23

    Naftilan, A. J., Pratt, R. E. & Dzau, V. J. J. clin. Invest. 83, 1419–1424 (1989).

  24. 24

    Darnell, J. E. Jr, Kerr, I. A. & Stark, G. R. Science 264, 1415–1421 (1994).

  25. 25

    Ihle, J. N. et al. Trends biochem. Sci. 19, 222–227 (1994).

  26. 26

    Laemmli, U. K. Nature 227, 680–685 (1970).

  27. 27

    Timmermans, P. B., Wong, P. C., Chiu, A. T. & Herblin, W. F. Trends pharmac. Sci 12, 55–62 (1991).

  28. 28

    Dignam, J. D., Lebovitz, R. M. & Roeder, R. Nucleic Acids Res. 11, 1475–1489 (1983).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Marrero, M., Schieffer, B., Paxton, W. et al. Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Nature 375, 247–250 (1995) doi:10.1038/375247a0

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.