PMID- 22734001
OWN - NLM
STAT- MEDLINE
DCOM- 20120831
LR  - 20211021
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 197
IP  - 7
DP  - 2012 Jun 25
TI  - Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression.
PG  - 907-19
LID - 10.1083/jcb.201109067 [doi]
AB  - Vascular cell adhesion molecule-1 (VCAM-1) plays important roles in development 
      and inflammation. Tumor necrosis factor-alpha (TNF-alpha) and focal adhesion kinase (FAK) 
      are key regulators of inflammatory and integrin-matrix signaling, respectively. 
      Integrin costimulatory signals modulate inflammatory gene expression, but the 
      important control points between these pathways remain unresolved. We report that 
      pharmacological FAK inhibition prevented TNF-alpha-induced VCAM-1 expression within 
      heart vessel-associated endothelial cells in vivo, and genetic or pharmacological 
      FAK inhibition blocked VCAM-1 expression during development. FAK signaling 
      facilitated TNF-alpha-induced, mitogen-activated protein kinase activation, and, 
      surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription 
      factor required for TNF-alpha-induced VCAM-1 production. FAK inhibition also 
      triggered FAK nuclear localization. In the nucleus, the FAK-FERM (band 4.1, 
      ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its 
      CHIP (C terminus of Hsp70-interacting protein) E3 ligase-dependent 
      polyubiquitination and degradation. These studies reveal new developmental and 
      anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production 
      via nuclear localization and promotion of GATA4 turnover.
FAU - Lim, Ssang-Taek
AU  - Lim ST
AD  - Department of Reproductive Medicine, University of California-San Diego, Moores 
      Cancer Center, La Jolla, CA 92093, USA. stlim@usouthal.edu
FAU - Miller, Nichol L G
AU  - Miller NL
FAU - Chen, Xiao Lei
AU  - Chen XL
FAU - Tancioni, Isabelle
AU  - Tancioni I
FAU - Walsh, Colin T
AU  - Walsh CT
FAU - Lawson, Christine
AU  - Lawson C
FAU - Uryu, Sean
AU  - Uryu S
FAU - Weis, Sara M
AU  - Weis SM
FAU - Cheresh, David A
AU  - Cheresh DA
FAU - Schlaepfer, David D
AU  - Schlaepfer DD
LA  - eng
GR  - 200810MFE-193594-139144/CAPMC/CIHR/Canada
GR  - R01 CA102310/CA/NCI NIH HHS/United States
GR  - GM087400/GM/NIGMS NIH HHS/United States
GR  - R01 HL103956/HL/NHLBI NIH HHS/United States
GR  - F32 CA159558/CA/NCI NIH HHS/United States
GR  - R01 GM087400/GM/NIGMS NIH HHS/United States
GR  - R01 HL093156/HL/NHLBI NIH HHS/United States
GR  - 1F32CA159558/CA/NCI NIH HHS/United States
GR  - HL093156/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (GATA4 Transcription Factor)
RN  - 0 (Gata4 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Ptk2 protein, mouse)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Cell Nucleus/*metabolism
MH  - Cells, Cultured
MH  - Embryo, Mammalian/metabolism
MH  - Enzyme Activation
MH  - Focal Adhesion Kinase 1/genetics/*metabolism
MH  - GATA4 Transcription Factor/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Ubiquitination
MH  - Vascular Cell Adhesion Molecule-1/*metabolism
PMC - PMC3384409
EDAT- 2012/06/27 06:00
MHDA- 2012/09/01 06:00
PMCR- 2012/12/25
CRDT- 2012/06/27 06:00
PHST- 2012/06/27 06:00 [entrez]
PHST- 2012/06/27 06:00 [pubmed]
PHST- 2012/09/01 06:00 [medline]
PHST- 2012/12/25 00:00 [pmc-release]
AID - jcb.201109067 [pii]
AID - 201109067 [pii]
AID - 10.1083/jcb.201109067 [doi]
PST - ppublish
SO  - J Cell Biol. 2012 Jun 25;197(7):907-19. doi: 10.1083/jcb.201109067.