Molecular cloning of the alpha subunit of human and guinea pig leukocyte adhesion glycoprotein Mo1: chromosomal localization and homology to the alpha subunits of integrins

Proc Natl Acad Sci U S A. 1988 Apr;85(8):2776-80. doi: 10.1073/pnas.85.8.2776.

Abstract

The cell-surface glycoprotein Mo1 is a member of the family of leukocyte cell adhesion molecules (Leu-CAMs) that includes lymphocyte function-associated antigen 1 (LFA-1) and p150,95. Each Leu-CAM is a heterodimer with a distinct alpha subunit noncovalently associated with a common beta subunit. Leu-CAMs play crucial roles in cell-cell and cell-matrix interactions. We describe the isolation and analysis of two partial cDNA clones encoding the alpha subunit of the Leu-CAM Mo1 in humans and guinea pigs. A monoclonal antibody directed against an epitope in the carboxyl-terminal portion of the guinea pig alpha chain was used for immunoscreening a lambda gt11 expression library. The sequence of a 378-base-pair insert from one immunoreactive clone revealed a single continuous open reading frame encoding 126 amino acids including a 26-amino acid tryptic peptide isolated from the purified guinea pig alpha subunit. A cDNA clone of identical size was isolated from a human monocyte/lymphocyte cDNA library by using the guinea pig clone as a probe. The human clone also encoded a 126-amino acid peptide including the sequence of an additional tryptic peptide present in purified human Mo1 alpha chain. RNA gel blots revealed that mature Mo1 alpha chain mRNA is approximately 5 kilobases in guinea pigs and humans. Southern analysis of DNA from hamster-human hybrids localized the human Mo1 alpha chain to chromosome 16, which has been shown to contain the gene for the alpha chain of lymphocyte function-associated antigen 1. A comparison of the Mo1 alpha chain coding region revealed significant homologies with carboxyl-terminal portions of the alpha subunits of fibronectin, vitronectin, and platelet IIb/IIIa receptors. These data suggest that the alpha subunits of Leu-CAMs evolved by gene duplication from a common ancestral gene and strengthen the hypothesis that the alpha subunits of these heterodimeric cell adhesion molecules on myeloid and lymphoid cells, platelets, and fibroblasts are evolutionary related.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blood Proteins / genetics*
  • Chromosomes, Human, Pair 16*
  • Cloning, Molecular
  • DNA / genetics
  • Guinea Pigs
  • Humans
  • Integrins
  • Macrophage-1 Antigen
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Receptors, Cell Surface / genetics*

Substances

  • Blood Proteins
  • Integrins
  • Macrophage-1 Antigen
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • DNA

Associated data

  • GENBANK/J03270
  • GENBANK/J03271
  • GENBANK/M18044
  • GENBANK/M19663
  • GENBANK/M19664
  • GENBANK/X07421