Vaccinia growth factor: newest member of the family of growth modulators which utilize the membrane receptor for EGF.

Abstract

A computer-aided search for structural homology between epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and sequences of proteins contained in the Dayhoff data base reveals a statistically significant homology with a peptide predicted to be encoded by an early gene of vaccinia virus (VV), a member of the poxvirus family. Fifteen residues of a 50 amino acid portion of this 140 residue VV polypeptide match residues in TGF-alpha; after insertion of a single gap, the vaccinia encoded polypeptide shares 19 residues with both EGF and urogastrone. Homologous regions contain six residues that correspond to the six cysteine residues of EGF and TGF-alpha that form disulphide bond mediated loop structures. A 25,000 Mr (apparent molecular weight) glycosylated polypeptide with the predicted functional activity, competing with EGF for binding to EGF membrane receptors, has been purified to homogeneity from VV infected Cercopithecus monkey kidney cell culture supernatants. This peptide, like both EGF and TGF-alpha, is a potent mitogen for appropriate target cells. Demonstration of a growth factor encoded by a DNA virus is unprecedented and may expand our understanding of DNA virus-host interactions.