Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho.
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a key role in cellular processes such as cell adhesion, migration, proliferation and survival. Recent studies have also implicated FAK in the regulation of cell-cell adhesion. Here, evidence is presented showing that siRNA-mediated suppression of FAK levels in NBT-II cells and expression of dominant negative mutants of FAK caused loss of epithelial cell morphology and inhibited the formation of cell-cell adhesions. Rac and Rho have been implicated in the regulation of cell-cell adhesions and can be regulated by FAK signaling. Expression of active Rac or Rho in NBT-II cells disrupted formation of cell-cell contacts, thus promoting a phenotype similar to FAK-depleted cells. The loss of intercellular contacts in FAK-depleted cells is prevented upon expression of a dominant negative Rho mutant, but not a dominant negative Rac mutant. Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This suggests that FAK regulates cell-cell contact formation by regulation of Rho.
Playford
Martin P
MP
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Vadali
Kavita
K
Cai
Xinming
X
Burridge
Keith
K
Schaller
Michael D
MD
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D048430:Cell Shape; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins
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