QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (37) Citing Articles via Google Scholar Google Scholar Articles by Yang, H. Articles by Raizada, M. K. Search for Related Content PubMed PubMed Citation Articles by Yang, H. Articles by Raizada, M. K.

 Previous Article  |  Next Article 

Volume 17, Number 5, Issue of March 1, 1997 pp. 1660-1669
Copyright ©1997 Society for Neuroscience

Involvement of MAP Kinase in Angiotensin II-Induced Phosphorylation and Intracellular Targeting of Neuronal AT₁ Receptors

Received Oct. 3, 1996; revised Dec. 9, 1996; accepted Dec. 10, 1996.

Hong Yang², Di Lu², Gavin P. Vinson¹, and Mohan K. Raizada²

¹ Department of Biochemistry, Queen Mary and Westfield College, London E1 4NS, England, and ² Department of Physiology, College of Medicine, University of Florida, Gainesville, Florida 32610

MAP kinase stimulation is a key signaling event in the AT₁ receptor (AT₁R)-mediated chronic stimulation of tyrosine hydroxylase and norepinephrine transporter in brain neurons by angiotensin II (Ang II). In this study, we investigated the involvement of MAP kinase in AT₁R phosphorylation to further our understanding of these persistent neuromodulatory actions of Ang II. Ang II caused a time-dependent phosphorylation of neuronal AT₁R. This phosphorylation was associated with internalization and translocation of AT₁R into the nucleus. MAP kinase also stimulated phosphorylation of neuronal AT₁R. The conclusion that MAP kinase participates in neuronal AT₁R phosphorylation and its targeting into the nucleus is supported further by the following. (1) MAP kinase-mediated phosphorylation of AT₁R was blocked by the AT₁R antagonist losartan; (2) AT₁R co-immunoprecipitated with MAP kinase; (3) MAP kinase-kinase inhibitor PD98059 attenuated Ang II-induced phosphorylation of AT₁R; and (4) PD98059 blocked Ang II-induced nuclear translocation of AT₁Rs. In summary, these observations demonstrate that Ang II-induced phosphorylation of AT₁R is mediated by its activation of MAP kinase. A possible role of AT₁R translocation into the nucleus on persistent neuromodulatory actions of Ang II has been discussed.

Key words: angiotensin II; AT₁ receptor; phosphorylation; nuclear receptor; nuclear localization signal (NLS); MAP kinase; hypothalamic-brainstem neurons

This article has been cited by other articles:

				F. Xiao, J. R Puddefoot, S. Barker, and G. P Vinson Changes in angiotensin II type 1 receptor signalling pathways evoked by a monoclonal antibody raised to the N-terminus J. Endocrinol., April 1, 2008; 197(1): 25 - 33. [Abstract] [Full Text] [PDF]

				C. Suarez, G. Diaz-Torga, A. Gonzalez-Iglesias, J. Vela, A. Mladovan, A. Baldi, and D. Becu-Villalobos Angiotensin II phosphorylation of extracellular signal-regulated kinases in rat anterior pituitary cells Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E645 - E653. [Abstract] [Full Text] [PDF]

				M. Seyedabadi, A. K. Goodchild, and P. M. Pilowsky Differential Role of Kinases in Brain Stem of Hypertensive and Normotensive Rats Hypertension, November 1, 2001; 38(5): 1087 - 1092. [Abstract] [Full Text] [PDF]

				H. Yang, X. Wang, and M. K. Raizada Characterization of Signal Transduction Pathway in Neurotropic Action of Angiotensin II in Brain Neurons Endocrinology, August 1, 2001; 142(8): 3502 - 3511. [Abstract] [Full Text] [PDF]

				J. Culman, J. Baulmann, A. Blume, and T. Unger Review: The renin-angiotensin system in the brain: an update Journal of Renin-Angiotensin-Aldosterone System, June 1, 2001; 2(2): 96 - 102. [PDF]

				O. S. Ruiz, R. B. Robey, Y.-Y. Qiu, L. J. Wang, C. J. Li, J. Ma, and J. A. L. Arruda Regulation of the renal Na-HCO3 cotransporter. XI. Signal transduction underlying CO2 stimulation Am J Physiol Renal Physiol, October 1, 1999; 277(4): F580 - F586. [Abstract] [Full Text] [PDF]

				F. L. Day, L. A. Rafty, C. N. Chesterman, and L. M. Khachigian Angiotensin II (ATII)-inducible Platelet-derived Growth Factor A-chain Gene Expression Is p42/44 Extracellular Signal-regulated Kinase-1/2 and Egr-1-dependent and Mediated via the ATII Type 1 but Not Type 2 Receptor. INDUCTION BY ATII ANTAGONIZED BY NITRIC OXIDE J. Biol. Chem., August 20, 1999; 274(34): 23726 - 23733. [Abstract] [Full Text] [PDF]

				H. Yang and M. K. Raizada Role of Phosphatidylinositol 3-Kinase in Angiotensin II Regulation of Norepinephrine Neuromodulation in Brain Neurons of the Spontaneously Hypertensive Rat J. Neurosci., April 1, 1999; 19(7): 2413 - 2423. [Abstract] [Full Text] [PDF]

				S. Apparsundaram, S. Schroeter, E. Giovanetti, and R. D. Blakely Acute Regulation of Norepinephrine Transport: II. PKC-Modulated Surface Expression of Human Norepinephrine Transporter Proteins J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 744 - 751. [Abstract] [Full Text]

				M. M. Muthalif, I. F. Benter, N. Karzoun, S. Fatima, J. Harper, M. R. Uddin, and K. U. Malik 20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells PNAS, October 13, 1998; 95(21): 12701 - 12706. [Abstract] [Full Text] [PDF]

				B. C. Yang, M. I. Phillips, D. Mohuczy, H. Meng, L. Shen, P. Mehta, and J. L. Mehta Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits Arterioscler. Thromb. Vasc. Biol., September 1, 1998; 18(9): 1433 - 1439. [Abstract] [Full Text] [PDF]

				H. Yang and M. K. Raizada MAP Kinase–Independent Signaling in Angiotensin II Regulation of Neuromodulation in SHR Neurons Hypertension, September 1, 1998; 32(3): 473 - 481. [Abstract] [Full Text] [PDF]

				R. D. Polakiewicz, S. M. Schieferl, L. F. Dorner, V. Kansra, and M. J. Comb A Mitogen-activated Protein Kinase Pathway Is Required for µ-Opioid Receptor Desensitization J. Biol. Chem., May 15, 1998; 273(20): 12402 - 12406. [Abstract] [Full Text] [PDF]

				D. Lu, H. Yang, and M. K. Raizada Involvement of p62 Nucleoporin in Angiotensin II-Induced Nuclear Translocation of STAT3 in Brain Neurons J. Neurosci., February 15, 1998; 18(4): 1329 - 1336. [Abstract] [Full Text] [PDF]

				D. Lu, H. Yang, and M. K. Raizada Attenuation of ANG II actions by adenovirus delivery of AT1 receptor antisense in neurons and SMC Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H719 - H727. [Abstract] [Full Text] [PDF]

				D. Lu, H. Yang, G. Shaw, and M. K. Raizada Angiotensin II-Induced Nuclear Targeting of the Angiotensin Type 1 (AT1) Receptor in Brain Neurons Endocrinology, January 1, 1998; 139(1): 365 - 375. [Abstract] [Full Text] [PDF]

				H. Yang, D. Lu, and M. K. Raizada Angiotensin II-Induced Phosphorylation of the AT1 Receptor From Rat Brain Neurons Hypertension, September 1, 1997; 30(3): 351 - 357. [Abstract] [Full Text]

				L. A. Ortiz, H. C. Champion, J. A. Lasky, F. Gambelli, E. Gozal, G. W. Hoyle, M. B. Beasley, A. L. Hyman, M. Friedman, and P. J. Kadowitz Enalapril protects mice from pulmonary hypertension by inhibiting TNF-mediated activation of NF-kappa B and AP-1 Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1209 - L1221. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help