Mutational analysis of the role of the carboxy-terminal region of the v-erbB protein in erythroid cell transformation.
The v-erbB protein encoded by the avian erythroblastosis virus AEV-H is responsible for the transformation of fibroblasts and erythroblasts by this virus. Deletion of amino acids 961-1102, which lie carboxy terminal to the kinase domain of the v-erbB protein, destroys the ability of the virus to transform erythroid cells without severely affecting fibroblast transformation. This region is termed the E-domain and has been postulated to contain a region important for erythroid cell transformation. In-frame deletions of approximately 23 amino acids were introduced throughout the E-domain in an attempt to locate a specific region that was essential for erythroid cell transformation. Several of the deletions gave rise to a partial transformed phenotype, although no single deletion that completely abolished erythroid cell transformation was found. Interestingly, deletion of amino acids 1031-1055 resulted in a superactivated v-erbB protein that was more active for erythroid cell transformation than the wild-type AEV-H v-erbB protein. This indicates that there is a negative regulatory region located within this region that normally partially suppresses the transforming activity of the v-erbB protein for erythroid cells. These data suggest that the E-domain contains both negative and positive regulatory regions that function in erythroid cells, and complete deletion of the region is necessary to abolish erythroid cell transformation.
Lee
E B
EB
Department of Microbiology, State University of New York, Stony Brook 11794.
Beug
H
H
Hayman
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D004900:Erythroblasts / Q000473:pathology*; D008969:Molecular Sequence Data; D009154:Mutation; D018739:Oncogene Proteins v-erbB; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D010766:Phosphorylation; D011817:Rabbits; D015682:Retroviridae Proteins, Oncogenic / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism
D018739:Oncogene Proteins v-erbB; D009856:Oncogene Proteins, Viral; D015682:Retroviridae Proteins, Oncogenic; D014443:Tyrosine