Abstract. The integrin ~6/34 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 as and/34 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of or6 is homologous to other integrin o~ chains (18-26% identity). Antibodies to an a6 carboxy terminus peptide immunoprecipitated 0t6~4 complexes from carcinoma cells and 0t6/31 complexes from platelets, providing further evidence for the association of ~6 with more than one t3 subunit. The deduced amino acid sequence of/34 predicts an extracellular portion homologous to other integrin/3 chains, and a unique cytoplasmic domain comprised of > 1,000 residues. This agrees with the structures of the ~4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. Organ.] J. 9:765-770). Compared to these structures, however, the /~4 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 ~4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of/34 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, 0t6~4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques. EMBO