The structural basis of localization and signaling by the focal adhesion targeting domain

Stefan Arold, Maria K. Hoellerer, Martin E M Noble

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The localization of focal adhesion kinase (FAK) to sites of integrin clustering initiates downstream signaling. The C-terminal focal adhesion targeting (FAT) domain causes this localization by interacting with talin and paxillin. FAT also mediates signaling through Grb2 via phosphorylated Y925. We report two crystal structures of the FAT domain. Large rearrangements of the structure are indicated to allow phosphorylation of Y925 and subsequent interaction with Grb2. Sequence homology and structural compatibility suggest a FAT-like fold for the C-terminal domains of CAS, Efs/Sin, and HEF1. A structure-based alignment including these proteins and the vinculin tail domain reveals a conserved region that could play a role in focal adhesion targeting. Previously postulated "paxillin binding subdomains" may contribute to structural integrity rather than directly to paxillin binding.

Original languageEnglish (US)
Pages (from-to)319-327
Number of pages9
JournalStructure
Volume10
Issue number3
DOIs
StatePublished - Mar 26 2002

Keywords

  • Crystallography
  • Focal adhesion kinase
  • Grb2
  • Integrin signaling
  • Paxillin binding
  • SH2 interactions

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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