Molecular Cloning and Tissue Expression ofFAT,the Human Homologue of theDrosophila fatGene That Is Located on Chromosome 4q34–q35 and Encodes a Putative Adhesion Molecule

Abstract

FAT,a new member of the human cadherin superfamily, has been isolated from the T-leukemia cell line J6. The predicted protein closely resembles theDrosophilatumor suppressor fat, which is essential for controlling cell proliferation duringDrosophiladevelopment. The gene has the potential to encode a large transmembrane protein of nearly 4600 residues 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 blotting analysis of J6 mRNA demonstrated full-length, approximately 15-kb,FATmessage in addition to several 5′-truncated transcripts. In addition to its presence in J6 cells, insituhybridization revealedFATmRNA expression in epithelia and in some mesenchymal compartments. Furthermore, higher levels of expression were observed in fetal, as opposed to adult, tissue, suggesting that its expression may be developmentally regulated in these tissues. FAT shows homologies with a number of proteins important in developmental decisions and cell:cell communication and is the first fat-like protein reported in vertebrates. The gene encodingFATwas located byin situhybridization on chromosome 4q34–q35. We propose that this family of molecules is likely to be important in mammalian developmental processes and cell communication.