JCB logo
Quantitative Colocalization Analysis Software
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 727K)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DeFea, K.A.
Right arrow Articles by Bunnett, N.W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DeFea, K.A.
Right arrow Articles by Bunnett, N.W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2000/3/1267/ $5.00
The Journal of Cell Biology, Volume 148, Number 6, March 20, 2000 1267-1282

Original Article

ß-Arrestin–dependent Endocytosis of Proteinase-activated Receptor 2 Is Required for Intracellular Targeting of Activated ERK1/2

K.A. DeFeaa, J. Zalevskyc, M.S. Thomaa, O. Dérya, R.D. Mullinsc, and N.W. Bunnetta,b
a Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660
b Department of Physiology, University of California, San Francisco, San Francisco, California 94143-0660
c Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143-0660

Correspondence to: K.A. DeFea, Box 0660, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0660. Tel:(415) 476-0935 Fax:(415) 476-0936 E-mail:defea{at}itsa.ucsf.edu.

Recently, a requirement for ß-arrestin–mediated endocytosis in the activation of extracellular signal–regulated kinases 1 and 2 (ERK1/2) by several G protein–coupled receptors (GPCRs) has been proposed. However, the importance of this requirement for function of ERK1/2 is unknown. We report that agonists of G{alpha}q-coupled proteinase–activated receptor 2 (PAR2) stimulate formation of a multiprotein signaling complex, as detected by gel filtration, immunoprecipitation and immunofluorescence. The complex, which contains internalized receptor, ß-arrestin, raf-1, and activated ERK, is required for ERK1/2 activation. However, ERK1/2 activity is retained in the cytosol and neither translocates to the nucleus nor causes proliferation. In contrast, a mutant PAR2 (PAR2{delta}ST363/6A), which is unable to interact with ß-arrestin and, thus, does not desensitize or internalize, activates ERK1/2 by a distinct pathway, and fails to promote both complex formation and cytosolic retention of the activated ERK1/2. Whereas wild-type PAR2 activates ERK1/2 by a PKC-dependent and probably a ras-independent pathway, PAR2({delta}ST363/6A) appears to activate ERK1/2 by a ras-dependent pathway, resulting in increased cell proliferation. Thus, formation of a signaling complex comprising PAR2, ß-arrestin, raf-1, and activated ERK1/2 might ensure appropriate subcellular localization of PAR2-mediated ERK activity, and thereby determine the mitogenic potential of receptor agonists.

Key Words: subcellular localization, MAP kinase, cytosol, receptor trafficking


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents