JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online August 25, 2008
doi:10.1083/jcb.200802145
The Journal of Cell Biology, Vol. 182, No. 4, 647-654
The Rockefeller University Press, 0021-9525 $30.00
© 2008 LeClaire et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2028K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
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
Google Scholar
Right arrow Articles by LeClaire, L. L.
Right arrow Articles by Barber, D. L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by LeClaire, L. L., III
Right arrow Articles by Barber, D. L.
Related Collections
Right arrowRelated In this Issue article
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?

Report

 Phosphorylation of the Arp2/3 complex is necessary to nucleate actin filaments

Lawrence L. LeClaire, III1, Martin Baumgartner1, Janet H. Iwasa2, R. Dyche Mullins2, and Diane L. Barber1

1 Department of Cell and Tissue Biology and 2 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Diane L. Barber: diane.barber{at}ucsf.edu

The actin-related protein 2/3 (Arp2/3) complex is the primary nucleator of new actin filaments in most crawling cells. Nucleation-promoting factors (NPFs) of the Wiskott-Aldrich syndrome protein (WASP)/Scar family are the currently recognized activators of the Arp2/3 complex. We now report that the Arp2/3 complex must be phosphorylated on either threonine or tyrosine residues to be activated by NPFs. Phosphorylation of the Arp2/3 complex is not necessary to bind NPFs or the sides of actin filaments but is critical for binding the pointed end of actin filaments and nucleating actin filaments. Mass spectrometry revealed phosphorylated Thr237 and Thr238 in Arp2, which are evolutionarily conserved residues. In cells, phosphorylation of only the Arp2 subunit increases in response to growth factors, and alanine substitutions of Arp2 T237 and T238 or Y202 inhibits membrane protrusion. These findings reveal an additional level of regulation of actin filament assembly independent of WASP proteins, and show that phosphorylation of the Arp2/3 complex provides a logical "or gate" capable integrating diverse upstream signals.

M. Baumgartner's present address is Vetsuisse Faculty, Department of Clinical Research and Veterinary Public Health, Section of Molecular Pathobiology, University of Bern, Bern CH-3012, Switzerland.

Abbreviations used in this paper: AP, Antarctic phosphatase; Arp, actin-related protein; NPF, nucleation-promoting factor; PP2C{alpha}, protein phosphatase 2C{alpha}; pThr, phosphothreonine; pTyr, phosphotyrosine; WASP, Wiskott-Aldrich syndrome protein.

© 2008 LeClaire et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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?

Related In this Issue article

Arp2/3 phosphorylation kickstarts cells
Mitch Leslie
J. Cell Biol. 2008 182: 617. [Full Text] [PDF]



This article has been cited by other articles:



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