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J. Biol. Chem., Vol. 276, Issue 20, 16597-16600, May 18, 2001
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From the Department of Biochemistry, Boston University School of
Medicine, Boston, Massachusetts 02118
Endothelins exert their biological effects
through G protein-coupled receptors. However, the precise mechanism of
downstream signaling and trafficking of the receptors is largely
unknown. Here we report that the histone acetyltransferase Tip60 and
the histone deacetylase HDAC7 interact with one of the ET receptors, ETA, as determined by yeast two-hybrid analysis, glutathione
S-transferase pull-down assays, and co-immunoprecipitation
from transfected COS-7 cells. In the absence of ET-1, Tip60 and HDAC7
were localized mainly in the cell nucleus while ETA was predominantly
confined to the plasma membrane. Stimulation with ET-1 resulted in the internalization of ETA to the perinuclear compartment and
simultaneously in the efflux of Tip60 and HDAC7 from the nucleus to the
same perinuclear compartment where each protein co-localized with the receptor. Upon co-transfection with ETA into COS-7 cells, Tip60 strongly increased ET-1-induced ERK1/2 phosphorylation, whereas HDAC7
had no significant effect. We thus suggest that protein acetylase and deacetylase interact with ETA in a
ligand-dependent fashion and may participate in ET signal transduction.
ACCELERATED PUBLICATION
Tip60 and HDAC7 Interact with the Endothelin Receptor A
and May Be Involved in Downstream Signaling*
,
*
This work was supported by Grants DK52057 and DK56736 from
the National Institutes of Health and by a research grant from the
American Diabetes Association (to K. V. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present Address: Parkinson's Inst., Sunnyvale, CA 94089.
§
Present Address: Millennium Pharmaceuticals, Cambridge, MA 02139.
¶
To whom correspondence should be addressed: 715 Albany St.,
Boston, MA 02118. Tel.: 617-638-5049; Fax: 617-638-5339; E-mail: kandror@biochem.bumc.bu.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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