Related Experiment Videos
Cleavage of focal adhesion kinase by caspases during apoptosis
1Department of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California 94305, USA.
Abstract:
Apoptotic cells undergo characteristic morphological changes that include detachment of cell attachment from the substratum and loss of cell-cell interactions. Attachment of cells to the extracellular matrix and to other cells is mediated by integrins. The interactions of integrins with the extracellular matrix activates focal adhesion kinase (FAK) and suppresses apoptosis in diverse cell types. Members of the tumor necrosis family such as Fas and Apo-2L, also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), induce apoptosis in both suspension and adherent cells through the activation of caspases. These caspases, when activated, cleave substrates that are important for the maintenance of nuclear and membrane integrity. In this study, we show that FAK is sequentially cleaved into two different fragments early in Apo-2L-induced apoptosis. We also demonstrate that FAK cleavage is mediated by caspases and that FAK shows unique sensitivity to different caspases. Our results suggest that disruption of FAK may contribute to the morphological changes observed in apoptotic suspension and adherent cells.
Insights
Focal adhesion kinase (FAK) is cleaved by caspases during Apo-2L-induced apoptosis. This cleavage may contribute to the morphological changes seen in apoptotic cells, impacting cell adhesion and integrity.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis involves cell detachment and loss of cell-cell interactions, mediated by integrins.
- Integrin interactions with the extracellular matrix activate focal adhesion kinase (FAK), suppressing apoptosis.
- Tumor necrosis factor family members, like Apo-2L (TRAIL), induce apoptosis via caspase activation.
Purpose of the Study:
- To investigate the role of FAK in Apo-2L-induced apoptosis.
- To determine if caspases cleave FAK during apoptosis.
- To understand FAK's contribution to apoptotic morphological changes.
Main Methods:
- Induction of apoptosis using Apo-2L (TRAIL).
- Analysis of FAK cleavage into distinct fragments.
- Assessment of caspase-mediated FAK cleavage and caspase specificity.
Main Results:
- FAK undergoes sequential cleavage into two fragments during Apo-2L-induced apoptosis.
- Caspases mediate the cleavage of FAK.
- FAK exhibits differential sensitivity to various caspases.
Conclusions:
- FAK cleavage by caspases is an early event in Apo-2L-induced apoptosis.
- Disruption of FAK function may drive the morphological alterations observed in apoptotic cells.
- FAK cleavage represents a potential mechanism contributing to apoptosis-associated cell detachment and loss of integrity.