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The dioxin receptor controls β1 integrin activation in fibroblasts through a Cbp-Csk-Src pathway
Javier Rey-Barroso1, Georgina P Colo, Alberto Alvarez-Barrientos
1Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain.
Cellular Signalling
|January 22, 2013
Summary
The dioxin receptor (AhR) regulates fibroblast migration by controlling β1 integrin activation. This process involves the C-terminal Src kinase-binding protein (Cbp) signaling pathway, impacting cell adhesion and movement.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Recent studies suggest the dioxin receptor (AhR) plays a role in cell adhesion and migration.
- Previous work established a link between AhR and cellular processes.
Purpose of the Study:
- To investigate the regulatory role of the C-terminal Src kinase-binding protein (Cbp) signaling pathway in β1 integrin activation.
- To determine if this mechanism is dependent on the dioxin receptor (AhR).
Main Methods:
- Utilized AhR knockout (AhR-/-) fibroblasts.
- Assessed β1 integrin activation using the 9EG7 anti-β1 mAb and a soluble fibronectin fragment.
- Examined talin-β1 association, fibronectin secretion, and cell migration.
- Manipulated Cbp expression in AhR-/- fibroblasts.
- Analyzed Src kinase activation and focal adhesion kinase (FAK) phosphorylation.
- Investigated the phosphorylation status of Cav1.
Main Results:
- AhR-/- fibroblasts exhibited higher β1 integrin activation, increased fibronectin secretion, and impaired directional migration.
- Interfering with Cbp expression in AhR-/- cells reduced β1 integrin activation, improved migration, and restored normal cell morphology.
- Cbp over-expression in AhR-/- cells led to reduced c-Src activation and FAK phosphorylation.
- AhR-/- cells showed hypophosphorylated Cav1, which was rescued by down-modulating Cbp.
Conclusions:
- The dioxin receptor (AhR) regulates fibroblast migration.
- AhR modulates β1 integrin activation through a Cbp-dependent, Src-mediated signaling pathway.
- This pathway is crucial for controlling cell adhesion, migration, and morphology.
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