Betacellulin

Betacellulin (BTC or beta-TC) is a member of the EGF family of cytokines which includes EGF, TGFα, amphiregulin, HB-EGF, epiregulin, tomoregulin and the neuregulins. All EGF famiy members are synthesized as type I transmembrane precursor proteins containing one or more EGF-like domains in their extracellular region. BTC, a heparin-binding protein, was originally isolated from the conditioned media of mouse pancreatic beta tumor cells as a 32 kDa glycoprotien. The mouse BTC cDNA encodes a 177 amino acid (aa) residue precursor with a 31 aa signal peptide, an 87 aa residue extracellular region containing one EGF-like domain, a 21 aa transmembrane domain and a 38 aa cytoplasmic domain. Soluble BTC is released from the transmembrane precursor by proteolytic processing. Mouse BTC shares 93% and 79% aa sequence identity with rat and human BTC, respectively. The mouse BTC gene is tightly linked to that of amphiregulin on mouse chromosome 5. BTC is expressed in most tissues including kidney, uterus, liver and pancreas. It is also present in body fluids including serum, milk and colostrum. BTC promotes pancreatic betacell growth and differentiation and is a potent mitogen for retinal pigment epithelial cells, vascular smooth muscle cells and fibroblasts. The effects of BTC is mediated by binding to ErbB1 and ErbB4 homodimers as well as ErbB heterodimers. Recombinant murine Betacellulin is a 9.0 kDa monomeric protein, containing 80 amino residues, which comprises the mature EGF homologous portion of the Betacellulin protein.