Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins.

Thumbnail
View / Download
213.7 Kb
Date
2001-12-18
Authors
Chen, W
Hu, LA
Semenov, MV
Yanagawa, S
Kikuchi, A
Lefkowitz, RJ
Miller, WE
Repository Usage Stats
207
views
127
downloads
Abstract
One aspect of the function of the beta-arrestins is to serve as scaffold or adapter molecules coupling G-protein coupled receptors (GPCRs) to signal transduction pathways distinct from traditional second messenger pathways. Here we report the identification of Dishevelled 1 and Dishevelled 2 (Dvl1 and Dvl2) as beta-arrestin1 (betaarr1) interacting proteins. Dvl proteins participate as key intermediates in signal transmission from the seven membrane-spanning Frizzled receptors leading to inhibition of glycogen synthase kinase-3beta (GSK-3beta), stabilization of beta-catenin, and activation of the lymphoid enhancer factor (LEF) transcription factor. We find that phosphorylation of Dvl strongly enhances its interaction with betaarr1, suggesting that regulation of Dvl phosphorylation and subsequent interaction with betaarr1 may play a key role in the activation of the LEF transcription pathway. Because coexpression of the Dvl kinases, CK1epsilon and PAR-1, with Dvl synergistically activates LEF reporter gene activity, we reasoned that coexpression of betaarr1 with Dvl might also affect LEF-dependent gene activation. Interestingly, whereas betaarr1 or Dvl alone leads to low-level stimulation of LEF (2- to 5-fold), coexpression of betaarr1 with either Dvl1 or Dvl2 leads to a synergistic activation of LEF (up to 16-fold). Additional experiments with LiCl as an inhibitor of GSK-3beta kinase activity indicate that the step affected by betaarr1 is upstream of GSK-3beta and most likely at the level of Dvl. These results identify betaarr1 as a regulator of Dvl-dependent LEF transcription and suggest that betaarr1 might serve as an adapter molecule that can couple Frizzled receptors and perhaps other GPCRs to these important transcription pathways.
Type
Journal article
Subject
Adaptor Proteins, Signal Transducing
Animals
Arrestins
Cell Line
DNA-Binding Proteins
Dishevelled Proteins
Humans
Lymphoid Enhancer-Binding Factor 1
Mice
Phosphoproteins
Phosphorylation
Protein Binding
Proteins
Transcription Factors
Transcription, Genetic
beta-Arrestins
Permalink
https://hdl.handle.net/10161/7809
Published Version (Please cite this version)
10.1073/pnas.211572798
Publication Info
Chen, W; Hu, LA; Semenov, MV; Yanagawa, S; Kikuchi, A; Lefkowitz, RJ; & Miller, WE (2001). beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. Proc Natl Acad Sci U S A, 98(26). pp. 14889-14894. 10.1073/pnas.211572798. Retrieved from https://hdl.handle.net/10161/7809.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
  • Scholarly Articles
More Info
Show full item record

Scholars@Duke

Chen

Wei Chen

Associate Professor in Medicine
My general area of interest relates to how cancer develops and how to identify cancer therapeutic agents. In particular I hope to identify molecular signals that underlie the changes necessary for directing normal tissue to a malignant state in cancer. Therefore, I have been studying how extracellular signals are deciphered by seven trans-membrane receptors and their regulatory proteins to control cell proliferation and differentiation. My major research focuses on studying GPCR, Smoothe
Lefkowitz

Robert J. Lefkowitz

James B. Duke Distinguished Professor of Medicine
Dr. Lefkowitz’s memoir, A Funny Thing Happened on the Way to Stockholm, recounts his early career as a cardiologist and his transition to biochemistry, which led to his Nobel Prize win. Robert J. Lefkowitz, M.D. is James B. Duke Professor of Medicine and Professor of Biochemistry and Chemistry at the Duke University Medical Center. He has been an Investigator of the
Alphabetical list of authors with Scholars@Duke profiles.
Open Access

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy

Rights for Collection: Scholarly Articles


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Related items

Showing items related by title, author, creator, and subject.

  • Thumbnail

    LKB1 Loss induces characteristic patterns of gene expression in human tumors associated with NRF2 activation and attenuation of PI3K-AKT. 

    Kaufman, Jacob M; Amann, Joseph M; Park, Kyungho; Arasada, Rajeswara Rao; Li, Haotian; Shyr, Yu; Carbone, David P (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014-06)
    Inactivation of serine/threonine kinase 11 (STK11 or LKB1) is common in lung cancer, and understanding the pathways and phenotypes altered as a consequence will aid the development of targeted therapeutic strategies. Gene ...
  • Thumbnail

    Amino acid permeases require COPII components and the ER resident membrane protein Shr3p for packaging into transport vesicles in vitro. 

    Kuehn, MJ; Schekman, R; Ljungdahl, PO (J Cell Biol, 1996-11)
    In S. cerevisiae lacking SHR3, amino acid permeases specifically accumulate in membranes of the endoplasmic reticulum (ER) and fail to be transported to the plasma membrane. We examined the requirements of transport of the ...
  • Thumbnail

    G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein. 

    Touhara, K; Hawes, BE; van Biesen, T; Lefkowitz, RJ (Proc Natl Acad Sci U S A, 1995-09-26)
    The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, ...

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University