Related Experiment Videos
Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage.
J Teixidó1, C M Parker, P D Kassner
1Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
The Journal of Biological Chemistry
|January 25, 1992
Summary
Cleavage of the alpha 4 subunit of VLA-4 (alpha 4 beta 1) integrin does not affect its cell adhesion functions. This finding clarifies the role of alpha 4 cleavage in T cell activation and immune responses.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- VLA-4 (alpha 4 beta 1) is an integrin receptor mediating cell adhesion.
- The alpha 4 subunit of VLA-4 can undergo cleavage, a process that increases upon T cell activation.
- The functional consequences of alpha 4 cleavage remain unclear.
Purpose of the Study:
- To investigate the functional significance of alpha 4 subunit cleavage in VLA-4-mediated adhesion.
- To compare the adhesion functions of VLA-4 with intact versus cleaved alpha 4 subunits.
Main Methods:
- Site-directed mutagenesis was used to create alpha 4 cDNA variants that prevent cleavage.
- Mutant and wild-type alpha 4 cDNAs were transfected into VLA-4-negative K562 cells.
- VLA-4-mediated adhesion to vascular cell adhesion molecule-1 and fibronectin was assessed.
Main Results:
- Mutagenesis successfully generated cells expressing either intact or cleaved alpha 4 subunits.
- Cells expressing intact or cleaved alpha 4 subunits exhibited similar VLA-4-dependent adhesion.
- Both intact and cleaved alpha 4 variants mediated equal cell aggregation in response to anti-alpha 4 antibodies.
Conclusions:
- Cleavage of the alpha 4 subunit does not alter known VLA-4-mediated adhesion functions.
- The functional role of alpha 4 cleavage in VLA-4 regulation requires further investigation.