Identification of betacellulin as a major peptide growth factor in milk: purification, characterization and molecular cloning of bovine betacellulin.
Betacellulin (BTC), a member of the epidermal growth factor (EGF) family of peptide growth factors, was purified from a growth-factor-enriched whey fraction of bovine milk by a combination of ion-exchange chromatography, gel-filtration chromatography, affinity chromatography and reverse-phase HPLC. Bovine BTC (bBTC) had an apparent molecular mass of 21-22 kDa on SDS/PAGE and exists in a glycosylated form. The cDNA encoding bBTC was obtained by a combination of 5' and 3' rapid amplification of cDNA ends ('RACE'). The primary translation product consists of 178 amino acid residues containing a putative signal sequence, a transmembrane domain, the mature BTC domain and a cytoplasmic domain containing a highly hydrophilic Arg-Lys-rich region similar to that of mouse BTC and human BTC. The amino acid sequence of the bBTC precursor was 88% identical with human BTC and 79% identical with mouse BTC. The bBTC gene was found to be expressed in a wide range of tissues, including the mammary gland. The identification of BTC in milk raises the possibility that it has a major role in the growth and development of the neonatal gastrointestinal tract.
Dunbar
A J
AJ
Cooperative Research Centre for Tissue Growth and Repair, CSIRO Health Sciences and Nutrition, Adelaide BC, SA 5000, Australia. andrew.dunbar@dhn.csiro.au
Priebe
I K
IK
Belford
D A
DA
Goddard
C
C
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D066259:Betacellulin; D001667:Binding, Competitive; D002417:Cattle; D002460:Cell Line; D003001:Cloning, Molecular; D004064:Digestive System / Q000254:growth & development / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006133:Growth Substances / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008894:Milk Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism
C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors