CLONING OF AN ALTERNATIVE FORM OF PLAKOGLOBIN (GAMMA-CATENIN) LACKING THE 4TH ARMADILLO REPEAT

Plakoglobin is a member of a protein family with a repeating amino acid motif called the armadillo repeat, and is a cytoplasmic protein found in both adherens junctions and desmosomes. Little is known about its function, but it has been shown to form distinct complexes with cadherins or desmosomal cadherins, Also, plakoglobin has been shown to form a complex with APC, a tumor suppressor gene product, We have isolated a cDNA clone encoding plakoglobin by means of the polymerase chain reaction (PCR) from a human transitional carcinoma cell line. The cDNA has the same nucleotide sequence as the previously published one [Franke et al. (1989) Proc. Natl. Acad, Sci. USA 86, 4027-4031], except that it has a deletion of 120 bp. The deleted sequence encodes the fourth armadillo repeat. Southern blot analysis of genomic DNA revealed that there is a single copy of the plakoglobin gene per haploid genome. Cloning and sequencing of a genomic DNA fragment containing the 120-bp deletion and the surrounding sequences revealed that these sequences are encoded by a single exon sequence. PCR amplification of the genomic DNA fragment of the corresponding region excluded the possible presence of the 120-bp deletion in the gene, Therefore the variant form is most likely derived through alternative splicing of precursor RNA transcripts in an exon sequence.