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10.1038/s41598-017-09495-5

http://scihub22266oqcxt.onion/10.1038/s41598-017-09495-5
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suck abstract from ncbi


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pmid28831165
      Sci+Rep 2017 ; 7 (1 ): 9033
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  • Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling #MMPMID28831165
  • Wan Q ; TruongVo T ; Steele HE ; Ozcelikkale A ; Han B ; Wang Y ; Oh J ; Yokota H ; Na S
  • Sci Rep 2017[Aug]; 7 (1 ): 9033 PMID28831165 show ga
  • Focal adhesion kinase (FAK) and Src family kinases (SFK) are known to play critical roles in mechanotransduction and other crucial cell functions. Recent reports indicate that they reside in different microdomains of the plasma membrane. However, little is known about their subcellular domain-dependent roles and responses to extracellular stimuli. Here, we employed fluorescence resonance energy transfer (FRET)-based biosensors in conjunction with collagen-coupled agarose gels to detect subcellular activities of SFK and FAK in three-dimensional (3D) settings. We observed that SFK and FAK in the lipid rafts and nonrafts are differently regulated by fluid flow and pro-inflammatory cytokines. Inhibition of FAK in the lipid rafts blocked SFK response to fluid flow, while inhibition of SFK in the non-rafts blocked FAK activation by the cytokines. Ex-vivo FRET imaging of mouse cartilage explants showed that intermediate level of interstitial fluid flow selectively decreased cytokine-induced SFK/FAK activation. These findings suggest that SFK and FAK exert distinctive molecular hierarchy depending on their subcellular location and extracellular stimuli.
  • |Animals [MESH]
  • |Biosensing Techniques [MESH]
  • |Cartilage/*metabolism [MESH]
  • |Cell Line [MESH]
  • |Collagen/*chemistry [MESH]
  • |Cytokines/*metabolism [MESH]
  • |Fluorescence Resonance Energy Transfer [MESH]
  • |Focal Adhesion Protein-Tyrosine Kinases/*metabolism [MESH]
  • |Humans [MESH]
  • |Imaging, Three-Dimensional [MESH]
  • |Mechanotransduction, Cellular [MESH]
  • |Membrane Microdomains/chemistry/metabolism [MESH]
  • |Mice [MESH]
  • |Signal Transduction [MESH]


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