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Focal Adhesion Kinase Orchestrates GLUT4 Translocation and Glucose Uptake via Cytoskeletal Turnover in Primary Adipocytes

Kopietz, Franziska LU orcid ; Neuhaus, Mathis LU orcid ; Borreguero-Muñoz, Andrea LU ; Kryvokhyzha, Dmytro LU orcid and Stenkula, Karin G. LU (2025) In FASEB Journal 39(10).
Abstract
ABSTRACT Intact insulin signaling and glucose transport in adipocytes are crucial to maintaining whole-body energy metabolism. Focal adhesion kinase stands as a central intracellular protein facilitating signaling between the extracellular matrix and the cytoplasm, thereby regulating cellular metabolism. Here, we have investigated the role of focal adhesion kinase in adipocyte glucose transport using an array of methods, including affinity purification combined with quantitative mass spectrometry, glucose tracer assays, western blotting, and confocal imaging. Pharmacological inhibition (PF-573228) of focal adhesion kinase suppressed the interaction of focal adhesion kinase with numerous actin-associated proteins, reduced Rac1 activity, as... (More)
ABSTRACT Intact insulin signaling and glucose transport in adipocytes are crucial to maintaining whole-body energy metabolism. Focal adhesion kinase stands as a central intracellular protein facilitating signaling between the extracellular matrix and the cytoplasm, thereby regulating cellular metabolism. Here, we have investigated the role of focal adhesion kinase in adipocyte glucose transport using an array of methods, including affinity purification combined with quantitative mass spectrometry, glucose tracer assays, western blotting, and confocal imaging. Pharmacological inhibition (PF-573228) of focal adhesion kinase suppressed the interaction of focal adhesion kinase with numerous actin-associated proteins, reduced Rac1 activity, as well as phosphorylation of the Rac1 downstream target PAK1/2, and further led to impaired GLUT4 translocation and glucose uptake. In summary, we demonstrate that focal adhesion kinase plays a key role in controlling actin remodeling, subsequent GLUT4 translocation, and ultimately glucose transport in adipocytes. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
actin, adipocytes, cytoskeleton, FAK, focal adhesion kinase, glucose uptake, GLUT4, insulin
in
FASEB Journal
volume
39
issue
10
article number
e70660
publisher
Wiley
external identifiers
  • pmid:40396386
  • scopus:105005855953
ISSN
0892-6638
DOI
10.1096/fj.202402764RR
language
English
LU publication?
yes
id
015c0816-0151-45fc-98fa-753a090d5a1c
date added to LUP
2025-05-21 13:19:30
date last changed
2025-06-12 04:02:18
@article{015c0816-0151-45fc-98fa-753a090d5a1c,
  abstract     = {{ABSTRACT Intact insulin signaling and glucose transport in adipocytes are crucial to maintaining whole-body energy metabolism. Focal adhesion kinase stands as a central intracellular protein facilitating signaling between the extracellular matrix and the cytoplasm, thereby regulating cellular metabolism. Here, we have investigated the role of focal adhesion kinase in adipocyte glucose transport using an array of methods, including affinity purification combined with quantitative mass spectrometry, glucose tracer assays, western blotting, and confocal imaging. Pharmacological inhibition (PF-573228) of focal adhesion kinase suppressed the interaction of focal adhesion kinase with numerous actin-associated proteins, reduced Rac1 activity, as well as phosphorylation of the Rac1 downstream target PAK1/2, and further led to impaired GLUT4 translocation and glucose uptake. In summary, we demonstrate that focal adhesion kinase plays a key role in controlling actin remodeling, subsequent GLUT4 translocation, and ultimately glucose transport in adipocytes.}},
  author       = {{Kopietz, Franziska and Neuhaus, Mathis and Borreguero-Muñoz, Andrea and Kryvokhyzha, Dmytro and Stenkula, Karin G.}},
  issn         = {{0892-6638}},
  keywords     = {{actin; adipocytes; cytoskeleton; FAK; focal adhesion kinase; glucose uptake; GLUT4; insulin}},
  language     = {{eng}},
  number       = {{10}},
  publisher    = {{Wiley}},
  series       = {{FASEB Journal}},
  title        = {{Focal Adhesion Kinase Orchestrates GLUT4 Translocation and Glucose Uptake via Cytoskeletal Turnover in Primary Adipocytes}},
  url          = {{http://dx.doi.org/10.1096/fj.202402764RR}},
  doi          = {{10.1096/fj.202402764RR}},
  volume       = {{39}},
  year         = {{2025}},
}