Small deletion in v-src SH3 domain of a transformation defective mutant of Rous sarcoma virus restores wild type transforming properties.
RSV mutant virus PA101T was obtained while assaying the tumorigenicity of parental PA101 virus in chickens. PA101 is a transformation defective mutant of RSV which has a low src kinase activity. However, PA101 retained a temperature-sensitive ability to induce sustained proliferation of neuroretina cells. PA101T appeared as a wild-type phenotype revertant of PA101. Molecular cloning and sequencing of PA101T showed that this reversion is due to additional mutations in PA101 src gene. These mutations are a deletion eliminating three amino acids in the N-terminal region of SH3 domain and mutation of Ala 426 to Val. Analysis of the properties of chimeric src genes associating either half of PA101T with the complementary regions of PA101 or wild-type virus showed that the N-terminal moiety of PA101T src, which contains the deletion, confers wild-type transforming properties, whereas its C-terminal moiety, which contains single amino acid mutation, confers a partially temperature-sensitive phenotype. These results are consistent with other reports showing that mutations or deletions in this region of SH3 activate the transforming potential of c-src. They support the hypothesis that the N-terminal region of SH3 interacts with a cellular negative regulator of src activity.
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Unité de Recherche Associée 1443 du CNRS, Institut Curie, Centre Universitaire, Orsay, France.
Barnier
J V
JV
Hampe
A
A
Laugier
D
D
Marx
M
M
Galibert
F
F
Calothy
G
G
D000595:Amino Acid Sequence; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D001483:Base Sequence; D002472:Cell Transformation, Viral; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D003673:Defective Viruses / Q000235:genetics*; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D011494:Protein Kinases / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014162:Transfection
D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src)