The primary structure of the alpha 4 subunit of VLA‐4: homology to other integrins and a possible cell‐cell adhesion function.

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 alpha 4 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 alpha 4 protein. The alpha 4 amino acid sequence was 17‐24% similar to other integrin alpha chains with known sequences. Parts of the alpha 4 sequence most conserved in other alpha 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, alpha 4 stands apart from all other known integrin alpha subunit sequences because (i) alpha 4 has neither an inserted I‐domain, nor a disulfide‐linked C‐terminal fragment, (ii) its sequence is the most unique and (iii) only alpha 4 has a potential protease cleavage site, near the middle of the coding region, which appears responsible for the characteristic 80,000 and 70,000 Mr fragments of alpha 4.