VLA-4 is a cell surface heterodimer in the integrin superfamily of adhesion receptors. Anti-VLA-4 antibodies inhibited cytolytic T cell activity, with inhibitory activity directed against the effector T cells rather than their targets. Thus, whereas other VLA receptors appear to mediate cell-matrix interactions, VLA-4 may have a cell-cell adhesion function. To facilitate comparative studies of VLA-4 and other integrins, cDNA clones for the human α4 subunit of VLA-4 were selected and then sequenced. The 3805 bp sequence encoded for 999 amino acids, with an N-terminus identical to that previously obtained from direct sequencing of purified α4 protein. The α4 amino acid sequence was 17-24% similar to other integrin α chains with known sequences. Part of the α4 sequence most conserved in other α chains include (i) the positions of 19/24 cysteine residues, (ii) three potential divalent cation binding sites of the general structure DXDXDGXXD and (iii) the transmembrane region. However, α4 stands apart from all other known integrin α subunit sequences because (i) α4 has neither an inserted I-domain, nor a disulfide-linked C-terminal fragment, (ii) its sequence is the most unique and (iii) only α4 has a potential protease cleavage site, near the middle of the coding region, which appears responsible for the characteristic 80000 and 70000 M(r) fragments of α4.
|Number of pages||8|
|Publication status||Published - 1989|
ASJC Scopus subject areas
- Cell Biology