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

The Journal of Cell Biology
Edward R HortonMartin J Humphries

Abstract

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.

References

Jun 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M D SchallerJ T Parsons
Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
May 1, 1995·Molecular and Cellular Biology·M D Schaller, J T Parsons
Jun 1, 1996·The Journal of Cell Biology·M Chrzanowska-Wodnicka, K Burridge
Jun 1, 1996·Journal of Leukocyte Biology·S M WahlJ B McCarthy
Mar 1, 1996·Analytical Chemistry·A ShevchenkoM Mann
May 12, 2000·Nature Cell Biology·D J SiegD D Schlaepfer
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·H B WangY Wang
Jan 22, 2003·The Biochemical Journal·Jenny BainPhilip Cohen
Feb 14, 2003·Journal of Cell Science·Jochen KirchnerBenjamin Geiger
May 14, 2003·The EMBO Journal·Cord Brakebusch, Reinhard Fässler
Jan 27, 2004·Nature Cell Biology·Donna J WebbAlan F Horwitz
May 17, 2005·Nature Cell Biology·Ellen J EzrattyGregg G Gundersen
Aug 22, 2006·Current Opinion in Cell Biology·Satyajit K Mitra, David D Schlaepfer
Feb 28, 2007·The Journal of Cell Biology·Markus SchoberElaine Fuchs
Mar 31, 2007·The Journal of Biological Chemistry·Jill K Slack-DavisJ Thomas Parsons
May 26, 2007·Science·Evan A Evans, David A Calderwood
Aug 3, 2007·Nature Cell Biology·Ronen Zaidel-BarBenjamin Geiger
Oct 20, 2007·Nature Protocols·Melissa S ClineGary D Bader
Nov 1, 2007·Nature Reviews. Molecular Cell Biology·Mark R MorganMark D Bass
Dec 7, 2007·The Journal of Cell Biology·Jonathan D HumphriesChristoph Ballestrem
Jul 16, 2008·Current Opinion in Pharmacology·Valerie G Brunton, Margaret C Frame
Dec 17, 2008·Nature Methods·Jianmin WuSampsa Hautaniemi
Sep 10, 2009·Science Signaling·Jonathan D HumphriesMartin J Humphries
Sep 30, 2009·Nature Reviews. Clinical Oncology·Lori C KimEric B Haura
Feb 13, 2010·The Journal of Biological Chemistry·Keefe T ChanAnna Huttenlocher

❮ Previous
Next ❯

Citations

Dec 9, 2016·International Journal of Molecular Sciences·Daniela BianconiGerald W Prager
Oct 11, 2016·Proteomics·Aki Manninen, Markku Varjosalo
Oct 11, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Andrew W HolleAdam J Engler
Jul 6, 2017·Cell Adhesion & Migration·Pavla RöselováKateřina Kuželová
Jun 4, 2017·Journal of Cell Science·Paul AthertonChristoph Ballestrem
Jan 13, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jiang-Yi HeQian Zhong
Feb 14, 2018·The Journal of Cell Biology·Tim B FessendenMargaret L Gardel
Jan 31, 2018·Oncogene·Jeremy S LogueRichard S Chadwick
Nov 28, 2017·Proteomics·Tian XiaJanine T Erler
Nov 2, 2016·Journal of Cell Science·Edward R HortonMartin J Humphries
Mar 18, 2017·Journal of Cell Science·Ben StutchburyChristoph Ballestrem
Jun 30, 2016·Journal of Cell Science·Adil R SarhanNeil A Hotchin
Oct 21, 2018·Journal of Cellular Physiology·Eunae YouSangmyung Rhee
May 2, 2019·The Journal of Membrane Biology·O Verdejo-TorresR G Contreras
Oct 28, 2019·Apoptosis : an International Journal on Programmed Cell Death·Ali M EthaebCamille Ettelaie
Apr 11, 2020·Medical Microbiology and Immunology·Daniel KummerKlaus Ebnet
Jul 17, 2020·The Journal of Clinical Investigation·Amanda K HuberBenjamin Levi
Feb 20, 2017·Journal of Hematology & Oncology·Ana María López-ColoméEdith López
Jun 12, 2019·Nature Reviews. Molecular Cell Biology·Jenny Z KechagiaPere Roca-Cusachs
Jun 23, 2018·The Journal of Cell Biology·Matthew C JonesMartin J Humphries
Dec 15, 2017·Cell Discovery·Jing ChenYanmei Tao
Jan 11, 2020·Frontiers in Molecular Biosciences·Rejina B Khan, Benjamin T Goult
Jan 13, 2021·Cell Biochemistry and Biophysics·Makhdoom SarwarJohn J Evans
Feb 6, 2021·BMC Cancer·Kristen A MarcellusBernard J Jasmin
Mar 11, 2021·PLoS Computational Biology·Joseph H R HetmanskiPatrick T Caswell
Apr 4, 2019·Experimental Cell Research·Thomas OrréGrégory Giannone
May 18, 2021·The Journal of Cell Biology·Erik S LinklaterRytis Prekeris
Sep 24, 2021·Journal of Cell Science·Ana E González WusenerCarlos O Arregui
Nov 5, 2021·Advanced Healthcare Materials·Maria RafaevaAlejandro E Mayorca-Guiliani

❮ Previous
Next ❯

Datasets Mentioned

BETA
PXD002720

Methods Mentioned

BETA
gene knockouts
FCS
ELISA
scraping
protein assay
affinity purification

Software Mentioned

Odyssey
Chemotaxis and Migration Tool
MATLAB
Mascot
Protein Interaction Network Analysis
Slidebook
Image Pro
MTrackJ
Prism
MetaVue

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.