This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meier, M. Articles by Feener, E. P. Search for Related Content PubMed PubMed Citation Articles by Meier, M. Articles by Feener, E. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections ACE/Angiotension receptors Cell signalling/signal transduction

(Hypertension. 2001;38:1260.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Angiotensin AT₁ Receptor Stimulates Heat Shock Protein 27 Phosphorylation In Vitro and In Vivo

Matthias Meier; George L. King; Allen Clermont; Alexandra Perez; Michio Hayashi; Edward P. Feener

From Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Mass.

Correspondence to Edward P. Feener, PhD, Research Division, Joslin Diabetes Center, One Joslin Pl, Boston, MA 02215. E-mail Edward.Feener{at}joslin.harvard.edu

The angiotensin type 1 receptor (AT₁) exerts a variety of its signaling and cellular actions through its effects on protein phosphorylation. Phosphoproteomic analysis of angiotensin (Ang) II–stimulated aortic smooth muscle cells revealed that heat shock protein 27 (HSP27) represents a major protein phosphorylation target of the AT₁ signaling pathway. Stimulation of cells with Ang II resulted in 1.7-fold (P<0.05) and 5.5-fold (P<0.001) increases in HSP27 phosphoisoforms at pI 5.7 and pI 5.4, respectively. This was accompanied by a 54% (P<0.01) decrease in the nonphosphorylated HSP27 isoform, located at pI 6.4. Treatment of samples with alkaline phosphatase reversed this redistribution of HSP27 phosphoisoforms. Ang II–stimulated HSP27 phosphorylation was completely blocked by pretreatment of cells with the AT₁ antagonist CV11974. Phosphoamino acid analysis demonstrated that Ang II–induced phosphorylation of both HSP27 phosphoisoforms occurred exclusively on serine. Protein kinase C inhibition completely blocked phorbol ester–induced HSP27 phosphorylation but did not impair Ang II–stimulated phosphorylation of HSP27, suggesting that AT₁ increased HSP27 phosphorylation by a protein kinase C–independent pathway. Intrajugular infusion of Ang II in rats increased HSP27 in aorta by 1.7-fold (P<0.02), and this response was inhibited by CV11974. These results suggest that Ang II–induced HSP27 phosphorylation is a physiologically relevant AT₁ signaling event. Because serine phosphorylation of HSP27 blocks its ability to cap F-actin, Ang II/AT₁–induced HSP27 phosphorylation may play a key role in actin filament remodeling required for smooth muscle cell migration and contraction.

Key Words: angiotensin II • aorta • heat shock proteins • phosphorylation • protein kinases • receptors, angiotensin II

This article has been cited by other articles:

				G.-X. Shi, L. Jin, and D. A. Andres Pituitary Adenylate Cyclase-Activating Polypeptide 38-Mediated Rin Activation Requires Src and Contributes to the Regulation of Hsp27 Signaling during Neuronal Differentiation Mol. Cell. Biol., August 15, 2008; 28(16): 4940 - 4951. [Abstract] [Full Text] [PDF]

				A. Zoubeidi, A. Zardan, E. Beraldi, L. Fazli, R. Sowery, P. Rennie, C. Nelson, and M. Gleave Cooperative Interactions between Androgen Receptor (AR) and Heat-Shock Protein 27 Facilitate AR Transcriptional Activity Cancer Res., November 1, 2007; 67(21): 10455 - 10465. [Abstract] [Full Text] [PDF]

				W. Huang, J. B. Fileta, T. Filippopoulos, A. Ray, A. Dobberfuhl, and C. L. Grosskreutz Hsp27 Phosphorylation in Experimental Glaucoma Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4129 - 4135. [Abstract] [Full Text] [PDF]

				X. Chen, H.-Y. Zhang, K. Pavlish, and J. N. Benoit Effects of chronic portal hypertension on small heat-shock proteins in mesenteric arteries Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G616 - G620. [Abstract] [Full Text] [PDF]

				Y. Chen, A.-P. Arrigo, and R. W. Currie Heat shock treatment suppresses angiotensin II-induced activation of NF-{kappa}B pathway and heart inflammation: a role for IKK depletion by heat shock? Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1104 - H1114. [Abstract] [Full Text] [PDF]

				D. J. Fernandes, R. W. Mitchell, O. Lakser, M. Dowell, A. G. Stewart, and J. Solway Invited Review: Do inflammatory mediators influence the contribution of airway smooth muscle contraction to airway hyperresponsiveness in asthma? J Appl Physiol, August 1, 2003; 95(2): 844 - 853. [Abstract] [Full Text] [PDF]