Significance of the gastrin homology and surrounding sequences in polyomavirus middle T antigen for cell transformation.
Deletion of residues 305 to 327 of polyomavirus middle T antigen, including the (Glu)6-Tyr-315 sequence that is a preferred site of phosphorylation in vitro by pp60c-src, markedly altered viral transformation of rat cells. The efficiency of transformation by the deletion mutant depended on how it was introduced into cells, and the resulting transformants displayed limited growth rates in monolayer and in suspension. Substitution of the polyomavirus residues 305 to 327 with a homologous region (containing [Glu]5-Ala-Tyr) from porcine gastrin did not restore wild-type transforming activity. These mutant middle T antigens interacted with pp60c-src and were phosphorylated in vitro. Thus, although a sequence of consecutive glutamic acid residues followed by a tyrosine is a dominant structural element which strongly influences the physical properties of middle T antigen, its presence did not ensure the biological activity of the protein. Other elements in this region of middle T antigen also contributed substantially to the transforming capacity of polyomavirus.
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D002460:Cell Line; D002472:Cell Transformation, Viral; D005755:Gastrins / Q000235:genetics*; D015688:Oncogene Protein pp60(v-src); D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011120:Polyomavirus / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D011994:Recombinant Proteins / Q000502:physiology; D012191:Retroviridae Proteins / Q000235:genetics / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D005755:Gastrins; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)