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Integrin-mediated signaling events in human endothelial cells
S M Short1, G A Talbott, R L Juliano
1Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Molecular Biology of the Cell
|August 7, 1998
Summary
Cell adhesion to fibronectin activates specific signaling pathways in endothelial cells, potentiating growth factor responses and contributing to anchorage-dependent cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Vascular endothelial cell function is regulated by extracellular matrix (ECM) interactions.
- Integrin-mediated adhesion plays a role in cell signaling, but its interplay with growth factors is not fully understood.
Purpose of the Study:
- To investigate how integrin-mediated anchorage to fibronectin affects growth factor signaling in human endothelial cells.
- To elucidate the role of cell adhesion in regulating downstream signaling kinases.
Main Methods:
- Human endothelial cells were cultured on fibronectin-coated surfaces or in suspension.
- Tyrosine phosphorylation of focal adhesion kinase (FAK), paxillin, and growth factor receptors was assessed.
- Mitogen-activated protein kinase (MAPK) and c-Jun kinase (JNK) activation by various agonists was measured in adherent vs. suspended cells.
Main Results:
- Adhesion to fibronectin induced tyrosine phosphorylation of FAK and paxillin, distinct from growth factor receptor autophosphorylation.
- Fibronectin adhesion activated MAPK independently and potentiated MAPK activation by growth factors, bombesin, lysophosphatidic acid (LPA), and tumor necrosis factor alpha (TNF-α).
- TNF-α-induced JNK activation was also enhanced in adherent cells.
Conclusions:
- Integrin-mediated adhesion and soluble mitogens cooperate to efficiently propagate signals to downstream kinases like MAPK and JNK.
- This cooperation likely contributes to the anchorage dependence of mitogenic cell cycle progression in endothelial cells.