Molecular cloning of the human α6 integrin subunit

We have isolated cDNAs encoding the α6 subunit from a γ gt11 expression library from human keratinocytes by combined screening with a rabbit polyclonal anti‐α6 antibody and the polymerase chain reaction. The α6 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 α6 were isolated, one of which is identical to the above cDNA. The two α6 subunits, called α6A and α6B, encoded by the two cDNAs each have a unique cytoplasmic domain, that of α6B being 18 amino acids longer than that of α6A. Different carcinoma cell lines contain transcripts for both α6 subunits. K 562 leukemic cells have little α6A or α6B mRNAs. The overall level of expression varies in the carcinoma cell lines, but reflects α6 cell surface expression. In A375 melanoma cells, however, cell surface expression of α6 was low in spite of a high level of mRNA. This suggests that other mechanisms may be involved in regulating the expression of α6 on the surface of these cells. The mRNA for both α6 subunits is around 6 kb. The α6 subunits are similar to other α subunits (26–31% identity with cleaved α subunits) of the integrin family but they are more similar to the α3 subunit (40% identity). This high degree of similarity may be the basis for their functional resemblance since both α3 and α6 subunits, when associated with β1, function as laminin receptors and bind to the long arm of laminin. The genes for α6 and β4, the alternative β subunit with which α6 combines on certain epithelial cells, were mapped to chromosome 2 and 17q11‐qter, respectively.