Molecular characterization of three erbB transducing viruses generated during avian leukosis virus-induced erythroleukemia: extensive internal deletion near the kinase domain activates the fibrosarcoma- and hemangioma-inducing potentials of erbB.
Three new erbB transducing viruses generated during avian leukosis virus-induced erythroblastosis have been cloned and sequenced, and their transforming abilities have been analyzed. Provirus 9134 E1 expresses an amino-terminally truncated erbB product that is analogous to the proviral insertionally activated c-erbB gag-erbB fusion product. This virus efficiently induces erythroblastosis, but does not transform fibroblasts in vitro or induce sarcomas in vivo. In contrast, virus 9134 S3 expresses an erbB product identical to the erbB product of 9134 E1, with the exception of a large internal deletion located between the kinase domain and the putative autophosphorylation site, P1. Interestingly, this virus is no longer capable of inducing erythroblastosis, but can induce both fibrosarcomas and hemangiomas in vivo. Provirus 9134 F3 has sustained an approximately 23-amino-acid carboxy-terminal truncation and is capable of inducing both erythroblastosis and sarcomagenesis. This virus expresses an erbB product with the shortest carboxy-terminal truncation sufficient to reveal the sarcomagenic potential of this protein. The distinct transforming properties of these viruses indicate that different structural domains of the erbB product confer distinct disease specificities.
Raines
M A
MA
Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
Maihle
N J
NJ
Moscovici
C
C
Moscovici
M G
MG
Kung
H J
HJ
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics* / Q000472:pathogenicity; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002645:Chickens; D003370:Coturnix; D005354:Fibrosarcoma / Q000209:etiology* / Q000235:genetics; D005814:Genes, Viral; D006391:Hemangioma / Q000209:etiology* / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000209:etiology* / Q000235:genetics; D007942:Leukemia, Experimental / Q000209:etiology* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D014161:Transduction, Genetic
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases