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A Novel Mode for Integrin-mediated Signaling: Tethering Is Required for Phosphorylation of FAK Y397

Mol. Biol. Cell, 1 October 2003
Vol. 14, Issue 10, p. 4306-4315
DOI: 10.1091/mbc.E03-01-0046

A Novel Mode for Integrin-mediated Signaling: Tethering Is Required for Phosphorylation of FAK Y397

  1. Qi Shi and
  2. David Boettiger*
  1. Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
  • Submitted January 27, 2003.
  • Revised May 7, 2003.
  • Accepted July 1, 2003.


The common model for integrin mediated signaling is based on integrin clustering and the potential for that clustering to recruit signaling molecules including FAK and src. The clustering model for transmembrane signaling originated with the analysis of the EGF receptor signaling and remains the predominant model. The roles for substrate-bound ligand and ligand occupancy in integrin-mediated signaling are less clear. A kinetic model was established using HT1080 cells in which there was a linear relationship between the strength of adhesion, the proportion of α5β1 integrin that could be chemically cross-linked, and the number of receptor-ligand bonds. This graded signal produced a similarly graded response measured by the level of specific phosphorylation of FAK Y397. FAK Y397 phosphorylation could also be induced by antibody bound to the substrate. In contrast, clustering of α5β1 on suspended cells with either antibody to β1 or by clustering of soluble ligand bound to α5β1 induced the phosphorylation of FAK Y861 but not Y397. There were no differences in signaling when activating antibodies were compared with blocking antibodies, presence or absence of ligand. Only tethering of α5β1 to the substrate was required for induction of FAK Y397 phosphorylation.


  • * Corresponding author. E-mail address: boettige{at}
  • Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E03–01–0046. Article and publication date are at

  • Monitoring Editor: Paul Matsudaira


Q. Shi and D. Boettiger, A Novel Mode for Integrin-mediated Signaling: Tethering Is Required for Phosphorylation of FAK Y397. Mol. Biol. Cell 14, 4306-4315 (2003).

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