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 Bornfeldt, K. E. Search for Related Content PubMed PubMed Citation Articles by Bornfeldt, K. E. Related Collections Cell signalling/signal transduction Gene expression Gene regulation Smooth muscle proliferation and differentiation Other Vascular biology

(Circulation Research. 2000;86:1101.)
© 2000 American Heart Association, Inc.

Editorials

Stressing Rac, Ras, and Downstream Heat Shock Protein 70

Karin E. Bornfeldt

From the Department of Pathology, University of Washington School of Medicine, Seattle, Wash.

Correspondence to Karin E. Bornfeldt, Department of Pathology, Box 357470, University of Washington School of Medicine, Seattle, WA 98195-7470. E-mail bornf@u.washington.edu

Key Words: G protein • mechanical strain • mitogen-activated protein kinases • smooth muscle • stress-activated protein kinase

	Introduction

 
Stress proteins (also known as heat shock proteins) regulate fundamental cellular processes, such as protein folding, protein sorting, protein degradation, assembly of proteins into larger complexes, and resolubilization of aggregates.^{1 2 3 4} Heat shock proteins (hsps) are divided into 6 subfamilies based on molecular mass: large hsps (110 to 100 kDa), hsp90, hsp70, hsp60, hsp40, and small hsps (30 to 18 kDa).⁵ Members of the hsp70 group are abundant in eukaryotic cells, and most research to date has focused on stress-inducible hsp70. hsp70 is induced by a number of stress stimuli, and its expression is regulated at the transcriptional level by heat shock transcription factor 1 (HSF1). HSF1, which normally exists as a monomer, trimerizes after activation and binds to a specific DNA recognition sequence (heat shock element) in the hsp70 promoter. HSF1 seems to require phosphorylation for full activity; however, the identity of the putative HSF1-activating kinase remains to be elucidated. It has been shown that HSF1 can be phosphorylated by extracellular signal–regulated protein kinases (ERKs) of the mitogen-activated protein kinase (MAPK) family in a Ras-dependent manner; however, this represses rather than stimulates transcriptional activity.^{6 7 8} It is also possible that HSF1 is activated by mechanisms that do not rely on phosphorylation, or that dephosphorylation of inhibitory phosphorylation sites stimulates the transcriptional activity of HSF1.

Although the first evidence of existence of hsps dates back to the early 1960s,⁹ hsps have recently received substantial attention in the field of cardiovascular research after several important and interesting observations. hsp70 has been shown to . . . [Full Text of this Article]

This article has been cited by other articles:

				X. Yin, N. J.D. Gower, H. A. Baylis, and K. Strange Inositol 1,4,5-Trisphosphate Signaling Regulates Rhythmic Contractile Activity of Myoepithelial Sheath Cells in Caenorhabditis elegans Mol. Biol. Cell, August 1, 2004; 15(8): 3938 - 3949. [Abstract] [Full Text] [PDF]

				J. Zhou, T. Schmid, R. Frank, and B. Brune PI3K/Akt Is Required for Heat Shock Proteins to Protect Hypoxia-inducible Factor 1{alpha} from pVHL-independent Degradation J. Biol. Chem., April 2, 2004; 279(14): 13506 - 13513. [Abstract] [Full Text] [PDF]

				F. Zhang, N. R. Hackett, G. Lam, J. Cheng, R. Pergolizzi, L. Luo, S. V. Shmelkov, J. Edelberg, R. G. Crystal, and S. Rafii Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells Blood, September 15, 2003; 102(6): 2115 - 2121. [Abstract] [Full Text] [PDF]