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PMID: 2424022 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Activation of the transforming potential of p60c-src by a single amino acid change.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 12 ·1986-06-00 ·Pages 4228-32

Levy JB, Iba H, Hanafusa H

Abstract

Previous work showed that overexpression of the cellular src (c-src) gene does not cause transformation of chicken cells in culture. However, viral stocks isolated from cells transfected with Rous sarcoma virus DNA containing the c-src gene in place of the viral src gene did occasionally produce foci. Virus obtained from these foci were highly transforming and appeared to arise via spontaneous mutation in the c-src-containing viral populations. The p60 proteins of the transforming mutant src viruses were found to have higher levels of in vitro tyrosine kinase activity than the levels observed with the parental viruses. In this study, we have molecularly cloned the src DNA sequences of two transforming mutant src viruses. When compared to the DNA sequence of the parental c-src viruses, the mutant viruses contain single point mutations that result in single amino acid changes in the src gene products (p60 proteins). Both amino acid changes reside in the tyrosine kinase domain of the protein. The mutation detected in one virus involves replacement of the normal Glu-378 in p60c-src by Gly, whereas the p60 of the other transforming virus has Phe instead of the normal Ile-441. Our data indicate that when p60c-src is expressed at elevated levels in a retroviral context, a single amino acid change in its primary sequence can activate the kinase activity of this protein and cause cellular transformation.

MeSH Terms
Amino Acid Sequence Animals Avian Sarcoma Viruses Base Sequence Cell Transformation, Neoplastic Cells, Cultured Chick Embryo Cloning, Molecular Genes Mutation Protein-Tyrosine Kinases/physiology Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins pp60(c-src) Structure-Activity Relationship
Chemicals
Proto-Oncogene Proteins Protein-Tyrosine Kinases Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Levy J B
Iba H
Hanafusa H
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41 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.12.4228
Published
1986-06-00
Pages
4228-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323705
Subset
IM
Grants
NIAID NIH HHS · AI07233 · United States
NCI NIH HHS · CA14935 · United States
NCI NIH HHS · CA18213 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.12.4228 PMC Full Text View journal details
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