Structure-function and biological role of betacellulin

Betacellulin (BTC) belongs to the epidermal growth factor (EGF) family of peptide ligands that are characterised by a six-cysteine consensus motif that forms three intra-molecular disulfide bonds crucial for binding the ErbB receptor family. BTC was initially described, purified and cloned from a mouse insulinoma cell line. ETC is proteolytically processed from a larger membrane-anchored precursor and is a potent mitogen for a wide variety of cell types, BTC binds and activates ErbB-1 and ErbB-4 homodimers and is further characterised by its unique ability to activate all possible heterodimeric ErbB receptors. ETC is widely expressed in most tissues and various body fluids, including milk. Expression is particularly high in the pancreas where it is thought to play a role in the differentiation of pancreatic beta cells. While much is known about the ErbB receptor binding characteristics of ETC and its effect on a variety of cultured cells under different conditions, the challenge that lies ahead is to determine the role of ETC in vivo. This review will focus on the structure of ETC and the various biological effects ascribed to this member of the EGF family. (C) 2000 Elsevier Science Ltd. All rights reserved.