Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility
Focal adhesion kinase (FAK) controls cellular adhesion and motility processes by its tight link to integrin- and extracellular-matrix-mediatedTo explore the dynamics of the regulation of FAK, we constructed a FRET-based probe that visualizes conformational rearrangements of the FERM domain of FAK in...
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219533_v122_n5_p656_Papusheva http://hdl.handle.net/20.500.12110/paper_00219533_v122_n5_p656_Papusheva |
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paper:paper_00219533_v122_n5_p656_Papusheva2023-06-08T14:43:43Z Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility Jares, Elizabeth Andrea FAK FERM conformation Force FRET Migration ROCK focal adhesion kinase integrin myosin adenosine triphosphatase myosin light chain kinase Rho kinase fluorescent dye focal adhesion kinase amino acid sequence animal cell article cell adhesion cell migration cell motility cell spreading conformational transition controlled study embryo enzyme regulation fibroblast culture fluorescence resonance energy transfer focal adhesion molecular probe mouse nonhuman priority journal protein analysis protein conformation protein domain protein function signal transduction animal cell adhesion cell culture cell motion chemistry cytology fibroblast focal adhesion genetics human metabolism mouse mutant physiology protein conformation Animals Cell Adhesion Cell Movement Cells, Cultured Fibroblasts Fluorescence Resonance Energy Transfer Fluorescent Dyes Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions Humans Mice Mice, Knockout Protein Conformation Signal Transduction Focal adhesion kinase (FAK) controls cellular adhesion and motility processes by its tight link to integrin- and extracellular-matrix-mediatedTo explore the dynamics of the regulation of FAK, we constructed a FRET-based probe that visualizes conformational rearrangements of the FERM domain of FAK in living cells. The sensor reports on an integrin-mediated conformational change in FAK following cellular adhesion. The perturbation is kinase-independent and involves the polybasic KAKTLR sequence in the FERM domain. It is manifested by an increased FRET signal and is expressed primarily in focal adhesions, and to a lesser extent in the cytoplasm. The conformational change in the FERM domain of FAK is observed in two consecutive phases during spreading - early and late - and is enriched in fully adhered motile cells at growing and sliding peripheral focal-adhesion sites, but not in stable or retracting focal adhesions. Inhibition of the actomyosin system indicates the involvement of tension signaling induced by Rho-associated kinase, rather than by myosin light-chain kinase, in the modulation of the FERM response. We conclude that the heterogeneous conformation of the FERM domain in focal adhesions of migrating cells reflects a complex regulatory mechanism for FAK that appears to be under the influence of cellular traction forces. Fil:Jares-Erijman, E.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219533_v122_n5_p656_Papusheva http://hdl.handle.net/20.500.12110/paper_00219533_v122_n5_p656_Papusheva |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
FAK FERM conformation Force FRET Migration ROCK focal adhesion kinase integrin myosin adenosine triphosphatase myosin light chain kinase Rho kinase fluorescent dye focal adhesion kinase amino acid sequence animal cell article cell adhesion cell migration cell motility cell spreading conformational transition controlled study embryo enzyme regulation fibroblast culture fluorescence resonance energy transfer focal adhesion molecular probe mouse nonhuman priority journal protein analysis protein conformation protein domain protein function signal transduction animal cell adhesion cell culture cell motion chemistry cytology fibroblast focal adhesion genetics human metabolism mouse mutant physiology protein conformation Animals Cell Adhesion Cell Movement Cells, Cultured Fibroblasts Fluorescence Resonance Energy Transfer Fluorescent Dyes Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions Humans Mice Mice, Knockout Protein Conformation Signal Transduction |
spellingShingle |
FAK FERM conformation Force FRET Migration ROCK focal adhesion kinase integrin myosin adenosine triphosphatase myosin light chain kinase Rho kinase fluorescent dye focal adhesion kinase amino acid sequence animal cell article cell adhesion cell migration cell motility cell spreading conformational transition controlled study embryo enzyme regulation fibroblast culture fluorescence resonance energy transfer focal adhesion molecular probe mouse nonhuman priority journal protein analysis protein conformation protein domain protein function signal transduction animal cell adhesion cell culture cell motion chemistry cytology fibroblast focal adhesion genetics human metabolism mouse mutant physiology protein conformation Animals Cell Adhesion Cell Movement Cells, Cultured Fibroblasts Fluorescence Resonance Energy Transfer Fluorescent Dyes Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions Humans Mice Mice, Knockout Protein Conformation Signal Transduction Jares, Elizabeth Andrea Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility |
topic_facet |
FAK FERM conformation Force FRET Migration ROCK focal adhesion kinase integrin myosin adenosine triphosphatase myosin light chain kinase Rho kinase fluorescent dye focal adhesion kinase amino acid sequence animal cell article cell adhesion cell migration cell motility cell spreading conformational transition controlled study embryo enzyme regulation fibroblast culture fluorescence resonance energy transfer focal adhesion molecular probe mouse nonhuman priority journal protein analysis protein conformation protein domain protein function signal transduction animal cell adhesion cell culture cell motion chemistry cytology fibroblast focal adhesion genetics human metabolism mouse mutant physiology protein conformation Animals Cell Adhesion Cell Movement Cells, Cultured Fibroblasts Fluorescence Resonance Energy Transfer Fluorescent Dyes Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions Humans Mice Mice, Knockout Protein Conformation Signal Transduction |
description |
Focal adhesion kinase (FAK) controls cellular adhesion and motility processes by its tight link to integrin- and extracellular-matrix-mediatedTo explore the dynamics of the regulation of FAK, we constructed a FRET-based probe that visualizes conformational rearrangements of the FERM domain of FAK in living cells. The sensor reports on an integrin-mediated conformational change in FAK following cellular adhesion. The perturbation is kinase-independent and involves the polybasic KAKTLR sequence in the FERM domain. It is manifested by an increased FRET signal and is expressed primarily in focal adhesions, and to a lesser extent in the cytoplasm. The conformational change in the FERM domain of FAK is observed in two consecutive phases during spreading - early and late - and is enriched in fully adhered motile cells at growing and sliding peripheral focal-adhesion sites, but not in stable or retracting focal adhesions. Inhibition of the actomyosin system indicates the involvement of tension signaling induced by Rho-associated kinase, rather than by myosin light-chain kinase, in the modulation of the FERM response. We conclude that the heterogeneous conformation of the FERM domain in focal adhesions of migrating cells reflects a complex regulatory mechanism for FAK that appears to be under the influence of cellular traction forces. |
author |
Jares, Elizabeth Andrea |
author_facet |
Jares, Elizabeth Andrea |
author_sort |
Jares, Elizabeth Andrea |
title |
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility |
title_short |
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility |
title_full |
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility |
title_fullStr |
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility |
title_full_unstemmed |
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility |
title_sort |
dynamic conformational changes in the ferm domain of fak are involved in focal-adhesion behavior during cell spreading and motility |
publishDate |
2009 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219533_v122_n5_p656_Papusheva http://hdl.handle.net/20.500.12110/paper_00219533_v122_n5_p656_Papusheva |
work_keys_str_mv |
AT jareselizabethandrea dynamicconformationalchangesinthefermdomainoffakareinvolvedinfocaladhesionbehaviorduringcellspreadingandmotility |
_version_ |
1768546100594081792 |