JCB logo
MBoC5 from Garland Science
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 10 May 2004. doi:10.1083/jcb.200311045
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 165, Number 3, 421-432
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
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
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lin, Y. H.
Right arrow Articles by Klemke, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, Y. H.
Right arrow Articles by Klemke, R. L.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
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?

Article

 Regulation of cell migration and survival by focal adhesion targeting of Lasp-1

Yi Hsing Lin1, Zee-Yong Park2, Dayin Lin2, Anar A. Brahmbhatt1, Marie-Christine Rio3, John R. Yates, III2, and Richard L. Klemke1

1 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
2 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037
3 Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France

Address correspondence to Richard L. Klemke, Dept. of Immunology, SP231, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-7750. Fax: (858) 784-7785. email: klemke{at}scripps.edu

Large-scale proteomic and functional analysis of isolated pseudopodia revealed the Lim, actin, and SH3 domain protein (Lasp-1) as a novel protein necessary for cell migration, but not adhesion to, the extracellular matrix (ECM). Lasp-1 is a ubiquitously expressed actin-binding protein with a unique domain configuration containing SH3 and LIM domains, and is overexpressed in 8–12% of human breast cancers. We find that stimulation of nonmotile and quiescent cells with growth factors or ECM proteins facilitates Lasp-1 relocalization from the cell periphery to the leading edge of the pseudopodium, where it associates with nascent focal complexes and areas of actin polymerization. Interestingly, although Lasp-1 dynamics in migratory cells occur independently of c-Abl kinase activity and tyrosine phosphorylation, c-Abl activation by apoptotic agents specifically promotes phosphorylation of Lasp-1 at tyrosine 171, which is associated with the loss of Lasp-1 localization to focal adhesions and induction of cell death. Thus, Lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ECM proteins.

Key Words: cell migration; apoptosis; signal transduction; focal adhesions; Abl tyrosine kinase

The online version of this article includes supplemental material.

Abbreviations used in this paper: Lasp-1, Lim, actin, and SH3 domain; MudPIT, multidimensional protein identification technology; SH3, Src homology domain 3; siRNA, small interfering RNA; TSA, trichostatin A.


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