The primary structure of the VLA-2/collagen receptor alpha 2 subunit (platelet GPIa): homology to other integrins and the presence of a possible collagen-binding domain.

Abstract

Abstract. VLA-2 (also called gpla/IIa on platelets) is a collagen receptor with a unique ot subunit and a subunit common to other adhesion receptors in the VLA/integrin family. Multiple cDNA clones for the human VLA-2 o~ 2 subunit have been selected from a hgtll library by specific antibody screening. The 5,374-bp nucleotide sequence encoded for 1,181 amino acids, including a signal peptide of 29 amino acids followed by a long extracellular domain (1,103 amino acids), a transmembrane domain, and a short cytoplasmic segment (22 amino acids). Direct sequencing of purified ot z protein confirmed the identity of the 15 NH2-terminal amino acids. Overall, the ot 2 amino acid sequence was 18-25% similar to the sequences known for other integrin ot subunits. In particular, the a2 sequence matched other integrin c~ chains in (a) the positions of 17 of its 20 cysteine residues; (b) the presence of three metal-binding domains of the general structure DXDXDGXXD; and (c) the transmembrane domain sequence. In addition, the ot 2 sequence has a 191-amino acid insert (called the 1-domain), previously found only in leukocyte integrins of the 82 integrin family. The oe 2 I-domain was 23-41% similar to domains in cartilage matrix protein and von Willebrand factor, which are perhaps associated with collagen binding. The NH2-terminal sequence reported here for c~ 2 does not match the previously reported o~ 2 NH2-terminal sequence (Takada, Y., J. L. Strominger, and M. E. Hemler. 1987. Proc. Natl. Acad. Sci. USA. 84:3239-3243). Resolution of this discrepancy suggests that there may be another VLA heterodimer that resembles VLA-2 in size but has a different amino acid sequence.

Complex patterns of expression suggest extensive roles for the α2β1 integrin in murine development

“…3) and found to be 82% homologous to nucleotides 1408-2594 of human a2 cDNA (Takada and Hemler, 1989). The deduced murine protein was 82% homologous and 92% similar to the human a2 protein (Fig.…”

“…The amino acid sequence is displayed below the nucleotide sequence. The nucleotide number is indicated on the left, and the amino acid number is indicated on the right according to the numbering system described by Takada and Hemler (1989). The putative metal binding sites are boxed, and the transmembrane domain is double underlined.…”

Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition

“…The derivation of CHO K1 cell transfectants expressing human ␣2 integrin subunit (CHO ␣2) or the PBJ-1 empty vector (CHO K1 PBJ-1) has been described previously (41)(42)(43)(44)(45). CHO cell transfectants were grown as for the parental cell line, except that G418 sulfate (Sigma) at 0.1-0.8 g/ml was included in the growth medium.…”

Collagen Receptor Control of Epithelial Morphogenesis and Cell Cycle Progression

“…The full-length human ␣ 2 integrin (X2C2) cDNA, the ␣ 2 cDNA lacking the cytoplasmic tail of the ␣ 2 integrin beyond the GFFKR sequence (X2C0), and the chimeric ␣ 2 cDNA containing the extracellular domain of ␣ 2 and the cytoplasmic tail of ␣ 4 (X2C4) in the expression vector pFneo were generous gifts from Dr. Martin Hemler (Harvard Medical School, Boston, MA). 21,22 The chimeric integrin cDNA containing the extracellular domain of ␣ 2 and the cytoplasmic tail of ␣ 1 was constructed by replacing the ␣ 4 cytoplasmic tail of the X2C4 construct with the ␣ 1 cytoplasmic tail. The ␣ 1 cytoplasmic tail was generated by annealing two complementary oligonucleotides representing base pairs 3916 to 3961 of the ␣ 1 integrin sequence.…”