A NEW ALTERNATIVE TRANSCRIPT ENCODES A 60 KDA TRUNCATED FORM OF INTEGRIN-BETA(3)

A cDNA for integrin beta(3) isolated from a human erythroleukaemia (HE L) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta(3C), results from the use of a cryptic AG donor splice si te in intron 8 of the beta(3) gene, and is different from a previously described alternative beta(3) mRNA. The predicted open reading frame of beta(3C) stops at a TAG stop codon 69 bp downstream from position 1 281. It starts with the signal peptide and the 404 N-terminal extracel lular residues of beta(3), encompassing the ligand binding sites, foll owed by 23 C-terminal intronderived residues, corresponding to a trunc ated form of beta(3) lacking the cysteine-rich, transmembrane and cyto plasmic domains. Expression of beta(3C) mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta(3C) transcript was also demonstrated in t he mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta(3C) alternative transcript was demonstrated in platelets by Western blotting using a polyclonal a ntibody raised against a synthetic peptide designed from the beta(3C) intronic sequence. Taken together, these results suggest a biological role for beta(3C) the first alternative transcript showing an altered extracellular domain of a beta integrin.