Regulation of cell migration and survival by focal adhesion targeting of Lasp-1 - Archive ouverte HAL
Article Dans Une Revue Journal of Cell Biology Année : 2004

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

Yihsing Lin
  • Fonction : Auteur
Zee-Yong Park
  • Fonction : Auteur
Dayin Lin
  • Fonction : Auteur
Anar A. Brahmbhatt
  • Fonction : Auteur
John R. Yates
  • Fonction : Auteur
Richard L. Klemke
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-04136965 , version 1 (21-06-2023)

Identifiants

Citer

Yihsing Lin, Zee-Yong Park, Dayin Lin, Anar A. Brahmbhatt, Marie-Christine Rio, et al.. Regulation of cell migration and survival by focal adhesion targeting of Lasp-1. Journal of Cell Biology, 2004, 165 (3), pp.421-432. ⟨10.1083/jcb.200311045⟩. ⟨hal-04136965⟩
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