Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print May 30, 2007
Mol. Biol. Cell 10.1091/mbc.E07-01-0013

A more recent version of this article appeared on August 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E07-01-0013v1
18/8/2960    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jiang, X.
Right arrow Articles by Wedegaertner, P. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, X.
Right arrow Articles by Wedegaertner, P. B.

Submitted on January 10, 2007
Revised on May 17, 2007
Accepted on May 23, 2007

Plasma Membrane and Nuclear Localization of G Protein-coupled Receptor Kinase 6A

Xiaoshan Jiang, Jeffrey L. Benovic, and Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107

Monitoring Editor: Jennifer Lippincott-Schwartz

G protein-coupled receptor (GPCR) kinases (GRKs) specifically phosphorylate agonist-occupied GPCRs at the inner surface of the plasma membrane (PM), leading to receptor desensitization. Here we show that the C-terminal 30 amino acids of GRK6A contain multiple elements that either promote or inhibit PM localization. Disruption of palmitoylation by individual mutation of cysteine 561, 562 or 565 or treatment of cells with 2-bromopalmitate shifts GRK6A from the PM to both the cytoplasm and nucleus. Likewise, disruption of the hydrophobic nature of a predicted amphipathic helix by mutation of two leucines to alanines at positions 551 and 552 causes a loss of PM localization. Moreover, acidic amino acids in the C-terminus appear to negatively regulate PM localization; mutational replacement of several acidic residues with neutral or basic residues rescues PM localization of a palmitoylation-defective GRK6A. Lastly, we characterize the novel nuclear localization, showing that nuclear export of nonpalmitoylated GRK6A is sensitive to leptomycin B and that GRK6A contains a potential nuclear localization signal. Our results suggest that the C-terminus of GRK6A contains a novel electrostatic palmitoyl switch in which acidic residues weaken the membrane binding strength of the amphipathic helix, thus allowing changes in palmitoylation to regulate PM versus cytoplasmic/nuclear localization.

Address correspondence to: Philip B. Wedegaertner (P_Wedegaertner{at}mail.jci.tju.edu)




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
J. S. Martini, P. Raake, L. E. Vinge, B. R. DeGeorge Jr., J. K. Chuprun, D. M. Harris, E. Gao, A. D. Eckhart, J. A. Pitcher, and W. J. Koch
Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes
PNAS, August 26, 2008; 105(34): 12457 - 12462.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.