Betacellulin(BTC),has been identified in the conditioned medium of cell lines derived from mouse pancreatic beta cell tumors. Betacellulin is a 32-kilodalton glycoprotein that appears to be processed from a larger transmembrane precursor by proteolytic cleavage. The carboxyl-terminal domain of betacellulin has 50 percent sequence similarity with that of rat transforming growth factor alpha. Betacellulin is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.Watanabe et al. purified soluble forms of human BTC to homogeneity from the conditioned medium of mouse A9 cells transfected with the human BTC precursor cDNA. Three types of soluble BTC, apparently derived from a single gene, were identified and their biologic activities assessed. Further studies suggested that the primary receptor for BTC is the EGFR.