Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition.

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Edward R. Horton, Jonathan D. Humphries, Ben Stutchbury, Guillaume Jacquemet, Christoph Ballestrem, Simon T. Barry, Martin J. Humphries
Publication year: 2016
Journal: Journal of Cell Biology
Journal acronym: J Cell Biol
Volume number: 212
Issue number: 3
Start page: 349
End page: 364
ISSN: 1540-8140


Integrin adhesion complexes (IACs) form mechanochemical connections between the extracellular matrix and actin cytoskeleton and mediate phenotypic responses via posttranslational modifications. Here, we investigate the modularity and robustness of the IAC network to pharmacological perturbation of the key IAC signaling components focal adhesion kinase (FAK) and Src. FAK inhibition using AZ13256675 blocked FAK(Y397) phosphorylation but did not alter IAC composition, as reported by mass spectrometry. IAC composition was also insensitive to Src inhibition using AZD0530 alone or in combination with FAK inhibition. In contrast, kinase inhibition substantially reduced phosphorylation within IACs, cell migration and proliferation. Furthermore using fluorescence recovery after photobleaching, we found that FAK inhibition increased the exchange rate of a phosphotyrosine (pY) reporter (dSH2) at IACs. These data demonstrate that kinase-dependent signal propagation through IACs is independent of gross changes in IAC composition. Together, these findings demonstrate a general separation between the composition of IACs and their ability to relay pY-dependent signals.

Last updated on 2020-09-04 at 08:06