title: Synthesis of an active hybrid growth factor (GF) in bacteria: transforming GF-alpha/vaccinia GF fusion protein.
abstract: A hybrid gene encoding for a polypeptide consisting of the first 33 N-terminal amino acid (aa) residues of transforming growth factor-alpha (TGF-alpha) and a C terminus consisting of 20 aa residues of vaccinia growth factor (VGF) was chemically synthesized and expressed as a fusion protein in Escherichia coli. The primary structure of the hybrid gene product maintained the same positioning of the three disulfide bonds found in each parent molecule thus conserving the first two loop regions of TGF-alpha and the third loop region of VGF. After cleavage with CNBr its renatured biological activity was found to be comparable to TGF-alpha and VGF with respect to binding to the epidermal growth factor receptor, stimulation of DNA synthesis and induction of anchorage-independent growth of NRK cells in the presence of TGF-beta. Thus, we suggest that similar domains can be interchanged within the same family of molecules and equivalent functionality maintained.
authors.affiliation: Oncogen, Seattle, WA 98121.
authors.forename: A F
authors.initials: AF
authors.lastname: Purchio
authors.forename: D R
authors.initials: DR
authors.lastname: Twardzik
authors.forename: A G
authors.initials: AG
authors.lastname: Bruce
authors.forename: L
authors.initials: L
authors.lastname: Wizental
authors.forename: L
authors.initials: L
authors.lastname: Madisen
authors.forename: J E
authors.initials: JE
authors.lastname: Ranchalis
authors.forename: S L
authors.initials: SL
authors.lastname: Hu
authors.forename: G
authors.initials: G
authors.lastname: Todaro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004274:DNA, Recombinant; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000235:genetics / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis*; D015291:Transforming Growth Factors
chemical_list: D004274:DNA, Recombinant; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C051087:vaccinia growth factor; D015291:Transforming Growth Factors