cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95.
The leukocyte adhesion receptors, p150,95, Mac-1 and LFA-1 are integral membrane glycoproteins which contain distinct alpha subunits of 180,000-150,000 Mr associated with identical beta subunits of 95,000 Mr in alpha beta complexes. p150,95 alpha subunit tryptic peptides were used to specify oligonucleotide probes and a cDNA clone of 4.7 kb containing the entire coding sequence was isolated from a size-selected myeloid cell cDNA library. The 4.7-kb cDNA clone encodes a signal sequence, an extracellular domain of 1081 amino acids containing 10 potential glycosylation sites, a transmembrane domain of 26 amino acids, and a C-terminal cytoplasmic tail of 29 residues. The extracellular domain contains three tandem homologous repeats of approximately 60 amino acids with putative divalent cation-binding sites, and four weaker repeats which lack such binding sites. The cDNA clone hybridizes with a mRNA of 4.7 kb which is induced during in vitro differentiation of myeloid cell lines. The p150,95 alpha subunit is homologous to the alpha subunits of receptors which recognize the RGD sequence in extracellular matrix components, as has previously been shown for the beta subunits, supporting the concept that receptors involved in both cell-cell and cell-matrix interactions belong to a single gene superfamily termed the integrins. Distinctive features of the p150,95 alpha subunit include an insertion of 126 residues N-terminal to the putative metal binding region and a deletion of the region in which the matrix receptors are proteolytically cleaved during processing.
Corbi
A L
AL
Laboratory of Membrane Immunochemistry, Dana-Farber Cancer Institute, Boston, MA 02115.
Miller
L J
LJ
O'Connor
K
K
Larson
R S
RS
Springer
T A
TA
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000378:metabolism
D000954:Antigens, Surface; D004273:DNA, Neoplasm; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances