Structure-function and biological role of betacellulin

Int J Biochem Cell Biol. 2000 Aug;32(8):805-15. doi: 10.1016/s1357-2725(00)00028-5.


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. BTC 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. BTC 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 BTC and its effect on a variety of cultured cells under different conditions, the challenge that lies ahead is to determine the role of BTC in vivo. This review will focus on the structure of BTC and the various biological effects ascribed to this member of the EGF family.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Betacellulin
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism
  • Gene Expression Regulation
  • Growth Substances / chemistry*
  • Growth Substances / genetics
  • Growth Substances / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Molecular Sequence Data
  • Protein Processing, Post-Translational
  • Structure-Activity Relationship


  • BTC protein, human
  • Betacellulin
  • Btc protein, mouse
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Epidermal Growth Factor
  • ErbB Receptors