cDNA and amino acid sequences of the cell adhesion protein receptor recognizing vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors

Proc Natl Acad Sci U S A. 1986 Nov;83(22):8614-8. doi: 10.1073/pnas.83.22.8614.

Abstract

Cells adhere to vitronectin substrates through a cell surface receptor that recognizes an Arg-Gly-Asp sequence in vitronectin. The receptor is a glycoprotein composed of a 150-kDa alpha and a 115-kDa beta subunit. The alpha subunit consists of two disulfide-bonded chains of 125 kDa and 25 kDa. cDNA clones were isolated for the alpha subunit of the vitronectin receptor from a phage lambda gt11 expression library made with RNA from a human fibroblast cell line, IMR-90. The identity of the clones that had been selected from the library based on immunological criteria was verified by comparison of DNA and protein sequences. NH2-terminal sequences were obtained for each of the alpha-subunit chains. The sequence of the 25-kDa chain of the alpha subunit was found in a cDNA clone, and the amino acid sequence deduced from the cDNA establishes the complete amino acid sequence of the 25-kDa chain. This chain contains a membrane-spanning domain as well as a putative intracytoplasmic region that is 32 amino acids long and consists mostly of polar amino acids. Comparison of the cDNA and protein sequences shows that the 25-kDa chain is generated by proteolytic cleavage of an alpha-subunit precursor, the partial sequence of which is contained in the cDNA clones. These clones contain 1910 base pairs of open reading frame and a 3' untranslated sequence. RNA blot hybridization detected one transcript of about 7 kilobases in RNA from fibroblastic and epithelial cells. Together, the cDNA clones cover 4442 bases of this RNA. The alpha-subunit sequence showed strong homology with the sequence of the alpha subunit of fibronectin receptor. Moreover, the NH2-terminal protein sequence of the 125-kDa chain was homologous with the NH2-terminal sequences of two other cell surface proteins, lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen 1 (Mac-1), which have been implicated as receptors for adhesion proteins of leukocytes. These results establish several of the structural features in the vitronectin receptor and suggest the existence of a superfamily of receptors for cell adhesion proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Surface / analysis
  • Antigens, Surface / metabolism*
  • Base Sequence
  • Cell Adhesion Molecules
  • DNA / analysis*
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • Platelet Membrane Glycoproteins / analysis
  • RNA, Messenger / analysis
  • Receptors, Fibronectin
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / genetics
  • Receptors, Vitronectin

Substances

  • Antigens, Surface
  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • Platelet Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Fibronectin
  • Receptors, Immunologic
  • Receptors, Vitronectin
  • DNA

Associated data

  • GENBANK/J02826
  • GENBANK/M14648
  • GENBANK/M18365