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Epidermal growth factor precursor is related to the translation product of the Moloney sarcoma virus oncogene mos
Abstract:
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 of 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 less than 2 X 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 normal murine and human DNA. Similarities are also observed between two 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 three 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.
Insights
The study reveals a significant evolutionary link between the precursor to epidermal growth factor (pro-EGF) and the mos oncogene family. This molecular similarity suggests a shared ancestry for pro-EGF and the EGF receptor.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Oncogene Research
Background:
- Epidermal Growth Factor (EGF) is synthesized as a large precursor protein (pro-EGF) that spans the cell membrane.
- The mos oncogene, specifically from Moloney murine sarcoma virus (v-mos), is known to be involved in cellular transformation.
Purpose of the Study:
- To investigate potential sequence similarities between pro-EGF and known viral oncogenes.
- To explore the evolutionary relationship between pro-EGF and the mos oncogene family.
Main Methods:
- Comparative sequence analysis of murine pro-EGF with translation products of viral oncogenes.
- Statistical evaluation of sequence similarities to determine significance.
- Examination of similarities with cellular homologues (c-mos) in murine and human DNA.
Main Results:
- A significant sequence similarity was found between the COOH-terminal region of v-mos and the cytoplasmic domain of pro-EGF (p < 2 X 10(-8)).
- Similarities were also identified between other regions of murine c-mos and the extracellular domain of pro-EGF.
- The mos oncogenes belong to the tyrosine kinase family, similar to the erbB oncogene.
Conclusions:
- The observed similarities between mos and pro-EGF suggest a common evolutionary origin.
- This relationship implies that pro-EGF and the EGF receptor may have evolved from a shared ancestral gene.
- The findings contribute to understanding the evolution of growth factor signaling pathways and oncogenes.