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

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

Research output: Contribution to journalArticlepeer-review

128 Scopus citations


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
Issue number3
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
We thank M. Ginsberg and A. Ducruix for the generous gift of expression vectors. We are grateful to M. Ginsberg and D. Schlaepfer for valuable discussions, to R. Aplin for mass spectrometric analysis of our samples, to I. Taylor for laboratory assistance, to R. Bryan and G. Coates for computing support, and to G. Labesse and D. Douget for help with homology modeling. We would also like to thank Dr. John Sinclair for help with molecular biology protocols. This work was supported by the Medical Research Council, component grant ID G9814322, and by infrastructure of the Oxford Centre for Molecular Sciences. S.T.A. is a fellow of the Medical Research Council, and M.K.H. is supported by the Wellcome Trust.


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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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