Molecular cloning of the human alpha 6 integrin subunit. Alternative splicing of alpha 6 mRNA and chromosomal localization of the alpha 6 and beta 4 genes

Eur J Biochem. 1991 Jul 15;199(2):425-33. doi: 10.1111/j.1432-1033.1991.tb16140.x.

Abstract

We have isolated cDNAs encoding the alpha 6 subunit from a lambda gt11 expression library from human keratinocytes by combined screening with a rabbit polyclonal anti-alpha 6 antibody and the polymerase chain reaction. The alpha 6 subunit encoded by this cDNA consists of 1050 amino acids with a 991-amino-acid extracellular, a 23-amino-acid transmembrane and a 36-amino-acid cytoplasmic domain. The extracellular domain contains three putative divalent cation-binding sites and nine potential N-linked glycosylation sites. From a cDNA library from normal human mammary gland cells two different cDNAs for alpha 6 were isolated, one of which is identical to the above cDNA. The two alpha 6 subunits, called alpha 6A and alpha 6B, encoded by the two cDNAs each have a unique cytoplasmic domain, that of alpha 6B being 18 amino acids longer than that of alpha 6A. Different carcinoma cell lines contain transcripts for both alpha 6 subunits. K562 leukemic cells have little alpha 6A or alpha 6B mRNAs. The overall level of expression varies in the carcinoma cell lines, but reflects alpha 6 cell surface expression. In A375 melanoma cells, however, cell surface expression of alpha 6 was low in spite of a high level of mRNA. This suggest that other mechanisms may be involved in regulating the expression of alpha 6 on the surface of these cells. The mRNA for both alpha 6 subunits is around 6 kb. The alpha 6 subunits are similar to other alpha subunits (26-31% identity with cleaved alpha subunits) of the integrin family but they are more similar to the alpha 3 subunit (40% identity). This high degree of similarity may be the basis for their functional resemblance since both alpha 3 and alpha 6 subunits, when associated with beta 1, function as laminin receptors and bind to the long arm of laminin. The genes for alpha 6 and beta 4, the alternative beta subunit with which alpha 6 combines on certain epithelial cells, were mapped to chromosome 2 and 17q11-qter, respectively.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Chromosome Banding
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • Chromosomes, Human, Pair 2*
  • Cloning, Molecular
  • Gene Library
  • Humans
  • Integrins / genetics*
  • Keratinocytes / physiology
  • Macromolecular Substances
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • RNA Splicing*
  • RNA, Messenger / genetics*
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid

Substances

  • Integrins
  • Macromolecular Substances
  • Oligonucleotide Probes
  • RNA, Messenger

Associated data

  • GENBANK/M60272
  • GENBANK/M60273
  • GENBANK/M60352
  • GENBANK/M60353
  • GENBANK/M60354
  • GENBANK/X56255
  • GENBANK/X56256
  • GENBANK/X56257
  • GENBANK/X57352
  • GENBANK/X59512