The ABC of BTC: structural properties and biological roles of betacellulin.
Betacellulin was initially detected as a growth-promoting factor in the conditioned medium of a mouse pancreatic β-cell tumor cell line. Sequencing of the purified protein and of the cloned cDNA supported the assumption that betacellulin is a new ligand of the epidermal growth factor receptor (EGFR), which was later confirmed experimentally. As a typical EGFR ligand, betacellulin is expressed by a variety of cell types and tissues, and the soluble growth factor is proteolytically cleaved from a larger membrane-anchored precursor. Importantly, BTC can - in addition to the EGFR - bind and activate all possible heterodimeric combinations of the related ERBB receptors including the highly oncogenic ERBB2/3 dimer, as well as homodimers of ERBB4. While a large number of studies attest a role for betacellulin in the differentiation of pancreatic β-cells, the last decade witnessed the association of betacellulin with a large number of additional biological processes, ranging from reproduction to the control of neural stem cells.
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.
Maik
M
Dahlhoff
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.
Eckhard
E
Wolf
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. Electronic address: schnder@lmb.uni-muenchen.de.
Marlon R
MR
Schneider
D000818:Animals; D066259:Betacellulin / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*
D066259:Betacellulin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
Angiogenesis; Betacellulin; Cancer; Cell signaling; Diabetes; Epidermal growth factor receptor; Growth factors