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.
Takada
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Y
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Elices
M J
MJ
Crouse
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Hemler
M E
ME
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D004247:DNA / Q000235:genetics; D006801:Humans; D016023:Integrins; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000235:genetics; D016029:Receptors, Very Late Antigen; D012689:Sequence Homology, Nucleic Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016023:Integrins; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016029:Receptors, Very Late Antigen; D004247:DNA