| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 22, 2001
Accepted on May 9, 2002
1 Department of Medical Biochemistry, Ehime University School of Medicine, Ehime, Japan CNRS UPR0415-Institut Cochin de Genetique Moleculaire, Paris, France
* To whom correspondence should be addressed. E-mail: horiuchi{at}m.ehime-u.ac.jp.
In the present study, we identified novel negative crosstalk between the angiotensin II subtype 2 (AT2) receptor and insulin receptor signaling in the regulation of phosphoinositide 3 kinase (PI 3-K), Akt and apoptosis in rat pheochromocytoma cell line, PC12W cells, which exclusively express AT2 receptor. We demonstrated that insulin-mediated insulin receptor substrate (IRS)-2-associated PI 3-K activity was inhibited by AT2 receptor stimulation, whereas IRS-1-associated PI 3-K activity was not significantly influenced. AT2 receptor stimulation did not change insulin-induced tyrosine-phosphorylation of IRS-2 or its association with the p85
subunit of PI 3-K, but led to a significant reduction of insulin-induced p85 phosphorylation. AT2 receptor stimulation increased the association of a protein tyrosine phosphatase, SHP-1, with IRS-2. Moreover we demonstrated that AT2 receptor stimulation inhibited insulin-induced Akt phosphorylation and that insulin-mediated anti-apoptotic effect was also blocked by AT2 receptor activation. Overexpression of a catalytically inactive dominant negative SHP-1 markedly attenuated the AT2 receptor-mediated inhibition of IRS-2-associated PI 3-K activity, Akt phosphorylation and anti-apoptotic effect induced by insulin. Taken together, these results indicate that AT2 receptor-mediated activation of SHP-1 and the consequent inhibition IRS-2-associated PI-3-K activity contributed at least partly to the inhibition of Akt phosphorylation, thereby inducing apoptosis.
This article has been cited by other articles:
 |
|
 |
|
  Y. Takami, H. Nakagami, R. Morishita, T. Katsuya, T.-X. Cui, T. Ichikawa, Y. Saito, H. Hayashi, Y. Kikuchi, T. Nishikawa, et al. Ubiquitin Carboxyl-Terminal Hydrolase L1, a Novel Deubiquitinating Enzyme in the Vasculature, Attenuates NF-{kappa}B Activation Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2184 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Giani, M. M. Gironacci, M. C. Munoz, C. Pena, D. Turyn, and F. P. Dominici Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1154 - H1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Li, M. Mogi, K. Tsukuda, H. Tomochika, J. Iwanami, L.-J. Min, C. Nahmias, M. Iwai, and M. Horiuchi Angiotensin II-Induced Neural Differentiation via Angiotensin II Type 2 (AT2) Receptor-MMS2 Cascade Involving Interaction between AT2 Receptor-Interacting Protein and Src Homology 2 Domain-Containing Protein-Tyrosine Phosphatase 1 Mol. Endocrinol., February 1, 2007; 21(2): 499 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Lee and L. Ragolia AKT phosphorylation is essential for insulin-induced relaxation of rat vascular smooth muscle cells Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1355 - C1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Plouffe, M.-O. Guimond, H. Beaudry, and N. Gallo-Payet Role of Tyrosine Kinase Receptors in Angiotensin II AT2 Receptor Signaling: Involvement in Neurite Outgrowth and in p42/p44mapk Activation in NG108-15 Cells Endocrinology, October 1, 2006; 147(10): 4646 - 4654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mogi, J.-M. Li, J. Iwanami, L.-J. Min, K. Tsukuda, M. Iwai, and M. Horiuchi Angiotensin II Type-2 Receptor Stimulation Prevents Neural Damage by Transcriptional Activation of Methyl Methanesulfonate Sensitive 2 Hypertension, July 1, 2006; 48(1): 141 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fu, J. Zhang, Y.-H. Tseng, T. Cui, X. Zhu, Y. Xiao, Y. Mou, H. De Leon, M. M.J. Chang, Y. Hamamori, et al. Rad GTPase Attenuates Vascular Lesion Formation by Inhibition of Vascular Smooth Muscle Cell Migration Circulation, March 1, 2005; 111(8): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.J. Landon and T. Inagami Beyond the G Protein: The Saga of the Type 2 Angiotensin II Receptor Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 15 - 16. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nouet, N. Amzallag, J.-M. Li, S. Louis, I. Seitz, T.-X. Cui, A.-M. Alleaume, M. Di Benedetto, C. Boden, M. Masson, et al. Trans-inactivation of Receptor Tyrosine Kinases by Novel Angiotensin II AT2 Receptor-interacting Protein, ATIP J. Biol. Chem., July 9, 2004; 279(28): 28989 - 28997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shiuchi, M. Iwai, H.-S. Li, L. Wu, L.-J. Min, J.-M. Li, M. Okumura, T.-X. Cui, and M. Horiuchi Angiotensin II Type-1 Receptor Blocker Valsartan Enhances Insulin Sensitivity in Skeletal Muscles of Diabetic Mice Hypertension, May 1, 2004; 43(5): 1003 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Okamoto, D. H. Sumida, C. R. O. Carvalho, A. M. Vargas, J. C. Heimann, B. D'A. Schaan, and U. F. Machado Changes in dietary sodium consumption modulate GLUT4 gene expression and early steps of insulin signaling Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2004; 286(4): R779 - R785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wu, M. Iwai, Z. Li, T. Shiuchi, L.-J. Min, T.-X. Cui, J.-M. Li, M. Okumura, C. Nahmias, and M. Horiuchi Regulation of Inhibitory Protein-{kappa}B and Monocyte Chemoattractant Protein-1 by Angiotensin II Type 2 Receptor-Activated Src Homology Protein Tyrosine Phosphatase-1 in Fetal Vascular Smooth Muscle Cells Mol. Endocrinol., March 1, 2004; 18(3): 666 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-J. Min, T.-X. Cui, Y. Yahata, K. Yamasaki, T. Shiuchi, H.-W. Liu, R. Chen, J.-M. Li, M. Okumura, T. Jinno, et al. Regulation of Collagen Synthesis in Mouse Skin Fibroblasts by Distinct Angiotensin II Receptor Subtypes Endocrinology, January 1, 2004; 145(1): 253 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Grishko, V. Pastukh, V. Solodushko, M. Gillespie, J. Azuma, and S. Schaffer Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2364 - H2372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Benndorf, R. H. Boger, S. Ergun, A. Steenpass, and T. Wieland Angiotensin II Type 2 Receptor Inhibits Vascular Endothelial Growth Factor-Induced Migration and In Vitro Tube Formation of Human Endothelial Cells Circ. Res., September 5, 2003; 93(5): 438 - 447. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
