EPITHELIAL INTEGRIN ALPHA-6BETA-4 - COMPLETE PRIMARY STRUCTURE OF ALPHA-6 AND VARIANT FORMS OF BETA-4

The integrin α6β4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the α6 and β4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of α6 is homologous to other integrin α chains (18-26% identity). Antibodies to an α6 carboxy terminus peptide immunoprecipitated α6β4 complexes from carcinoma cells and α6β2 complexes from platelets, providing further evidence for the association of α6 with more than one β subunit. The deduced amino acid sequence of β4 predicts an extracellular portion homologous to other integrin β chains, and a unique cytoplasmic domain comprised of >1,000 residues. This agrees with the structures of the β4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A.E.G.Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the β4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of β4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of β4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, α6β4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.