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Mol. Biol. Cell 14 (10): 4306-4315

Copyright © 2003 by The American Society for Cell Biology.

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

Qi Shi, and David Boettiger *

Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received for publication January 27, 2003. Revision received May 7, 2003. Accepted for publication July 1, 2003.

Monitoring Editor: Paul Matsudaira

Abstract: 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 {alpha}5{beta}1 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 {alpha}5{beta}1 on suspended cells with either antibody to {beta}1 or by clustering of soluble ligand bound to {alpha}5{beta}1 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 {alpha}5{beta}1 to the substrate was required for induction of FAK Y397 phosphorylation.

Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E03–01–0046. Article and publication date are at

* Corresponding author. E-mail address: boettige{at}

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