Cloning and characterization of a novel integrin beta(3) subunit

We have identified a novel integrin beta(3) subunit, termed beta(3C), from a human osteoclast cDNA library. The COOH-terminal sequence and 5'-untranslated region of the beta(3C) subunit differs from the previously reported beta(3A) (platelet) and beta(3B) (placenta) sequences, while the regions coding for the transmembrane and extracellular domains are identical. The beta(3C) cytoplasmic domain contains 37 amino acids, the last 17 of which are encoded by a novel exon located about 6 kilobase pairs downstream of exon 14 of the beta(3A) gene. HEK 293 cells were stably co-transfected with alpha(V) and either beta(3C) (HEK beta(3C)) or beta(3A) (HEK beta(3A). The viability of HER beta(3C) cells was lower than that of HER beta(3A) cells, and HEH beta(3C) cells in culture grew as clusters rather than as a monolayer. The novel cytoplasmic domain did not affect receptor binding affinity; both alpha(V) beta(3A) and alpha(V) beta(3C) isoforms exhibited high affinity binding to I-125-echistatin and cyclic and linear RGD peptides. However, in contrast to HEK beta(3A) HEK beta(3C) cells failed to adhere to osteopontin, an alpha(V) beta(3) matrix protein. The data provide further support for the key role of the cytoplasmic domain of the beta(3) integrin in cell adhesion and suggest a potential role for the beta(3C) integrin subunit in modulating cell-matrix interactions.