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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Detalles Bibliográficos
Autor principal: Jares, Elizabeth Andrea
Publicado: 2009
Materias:
FAK
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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spelling 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
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