Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.
The integrin alpha 6 beta 4 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 alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 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 beta 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 beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.
Tamura
R N
RN
Department of Immunology, IMM-8, Research Institute of Scripps Clinic, La Jolla, California 92037.
Rozzo
C
C
Starr
L
L
Chambers
J
J
Reichardt
L F
LF
Cooper
H M
HM
Quaranta
V
V
D000595:Amino Acid Sequence; D001483:Base Sequence; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000737:chemistry* / Q000235:genetics*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011061:Poly A / Q000032:analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D016023:Integrins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011061:Poly A