MOLECULAR-CLONING AND TISSUE EXPRESSION OF FAT, THE HUMAN HOMOLOG OF THE DROSOPHILA FAT GENE THAT IS LOCATED ON CHROMOSOME 4Q34-Q35 AND ENCODES A PUTATIVE ADHESION MOLECULE

FAT, a new member of the human cadherin superfamily, has been isolated from the T-leukemia cell line J6. The predicted protein closely resem bles the Drosophila tumor suppressor fat, which is essential for contr olling cell proliferation during Drosophila development. The gene has the potential to encode a large transmembrane protein of nearly 4600 r esidues with 34 tandem cadherin repeats, five EGF-like repeats, and a laminin A-G domain. The cytoplasmic sequence contains two domains with distant homology to the cadherin catenin-binding region. Northern blo tting analysis of J6 mRNA demonstrated full-length, approximately 15-k b, FAT message in addition to several 5'truncated transcripts. In addi tion to its presence in J6 cells, in situ hybridization revealed FAT m RNA expression in epithelia and in some mesenchymal compartments. Furt hermore, higher levels of expression were observed in fetal, as oppose d to adult, tissue, suggesting that its expression may be developmenta lly regulated in these tissues. FAT shows homologies with a number of proteins important in developmental decisions and cell:cell communicat ion and is the first fat-like protein reported in vertebrates. The gen e encoding FAT was located by in situ hybridization on chromosome 4q34 -q35. We propose that this family of molecules is likely to be importa nt in mammalian developmental processes and cell communication. (C) 19 95 Academic Press, Inc.