EPIDERMAL GROWTH-FACTOR PRECURSOR IS RELATED TO THE TRANSLATION PRODUCT OF THE MOLONEY SARCOMA-VIRUS ONCOGENE MOS

Murine epidermal growth factor (EGF) is synthesized as part of a large precursor (pro-EGF), which is thought to span the cell membrane. Comparison of the published pro-EGF sequence with the sequences of the translation products of viral oncogenes reveals that pro-EGF is related to the translation product of mos, the oncogene of Moloney murine sarcoma virus. Similarity is greatest between the COOH-terminal region v-mos (residues 317-360) and part of the cytoplasmic domain of pro-EGF (residues 1127-1174). Statistical comparison of these sequences indicates that the probability of the similarity arising by chance is < 2 .times. 10-8. This similarity extends to the corresponding regions of the translation products of the cellular homologues (c-mos) of the v-mos gene present in nomal murine and human DNA. Similarities are also observed between 2 other regions of the murine c-mos sequence (residues 48-134 and 196-275) and parts of the extracellular domain of pro-EGF (residues 565-651 and 741-817, respectively). All 3 mos genes are members of the tyrosine kinase family of oncogenes, as is erbB, the oncogene of avian erythroblastosis virus. Since the sequences of the erbB translation product and the EGF receptor are closely related, the relationship between mos and pro-EGF suggests that pro-EGF and the EGF receptor have evolved from a common ancestor.