Structure‐function analysis of the human integrin VLA‐4 (α4/β1)

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Abstract
The structure-function relationship of the human integrin VLA-4 (α4/β1; CD49d/CD29), has been studied in the human B-cell line Ramos by immunochemical and functional analysis. Ramos cells expressed the 150-kDa non-proteolyzed form of the α4 chain, which could be digested upon mild trypsin treatment to generate the 80- and 65-kDa proteolyzed forms, as well as α4 polypeptides of 55 and 50 kDa. In addition, treatment of Ramos cells with high doses of pronase predominantly yielded the 55- and 50-kDa α4 peptides. The trypsin-generated 80- and 65-kDa α4 polypeptides, but not the 55- and 50-kDa fragments, were able to associate with the β1 chain. Distinct anti-VLA-4 mAb against four different α4 epitopes, referred to as epitopes A, B1, B2, and C, recognized the 150-kDa α4 chain both associated or non-associated with the β1 chain. The α4 proteolytic forms of 80, 65 and 50 kDa were precipitated by the anti-α4 mAb directed against the four different α4 epitopes. On the other hand, the 55-kDa α4 peptide was present in precipitates from anti-α4 mAb specific for epitopes A, B1 and C, but absent in precipitates from the anti-α4 mAb specific for epitope B2. The different adhesive capacities of the VLA-4 integrin, namely the interaction with a 38-kDa fibronectin fragment containing the CS-1 region of plasma fibronectin (Fn-38), the binding to the vascular cell adhesion molecule-1 (VCAM-1), or the ability to mediate the anti-α4-induced cell aggregation, were not altered on VLA-4 from cells upon mild trypsin treatment, when compared to non-treated cells. However, the 55- and 50-kDa α4 forms generated by high-dose pronase cell treatment, failed to mediate cell interaction with Fn-38 or VCAM-1 ligands, and cell aggregation could not be triggered through VLA-4 under these conditions.

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