Eb. Lee et al., MUTATIONAL ANALYSIS OF THE ROLE OF THE CARBOXY-TERMINAL REGION OF THEV-ERBB PROTEIN IN ERYTHROID CELL-TRANSFORMATION, Oncogene, 8(5), 1993, pp. 1317-1327
The v-erbB protein encoded by the avian erythroblastosis virus AEV-H i
s responsible for the transformation of fibroblasts and erythroblasts
by this virus. Deletion of amino acids 961-1102, which lie carboxy ter
minal 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 trans
formation. In-frame deletions of approximately 23 amino acids were int
roduced throughout the E-domain in an attempt to locate a specific reg
ion that was essential for erythroid cell transformation. Several of t
he deletions gave rise to a partial transformed phenotype, although no
single deletion that completely abolished erythroid cell transformati
on was found. Interestingly, deletion of amino acids 1031-1055 resulte
d in a superactivated v-erbB protein that was more active for erythroi
d cell transformation than the wild-type AEV-H v-erbB protein. This in
dicates that there is a negative regulatory region located within this
region that normally partially suppresses the transforming activity o
f the v-erbB protein for erythroid cells. These data suggest that the
E-domain contains both negative and positive regulatory regions that f
unction in erythroid cells, and complete deletion of the region is nec
essary to abolish erythroid cell transformation.