title: 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.
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.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: F
authors.initials: F
authors.lastname: Hogervorst
authors.forename: I
authors.initials: I
authors.lastname: Kuikman
authors.forename: A G
authors.initials: AG
authors.lastname: van Kessel
authors.forename: A
authors.initials: A
authors.lastname: Sonnenberg
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D015723:Gene Library; D006801:Humans; D016023:Integrins / Q000235:genetics*; D015603:Keratinocytes / Q000502:physiology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
chemical_list: D016023:Integrins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D012333:RNA, Messenger