Truncation of the human EGF receptor leads to differential transforming potentials in primary avian fibroblasts and erythroblasts.
The transforming capacity of the normal and mutant human EGF receptor (EGFR) was investigated in primary chicken cells. In fibroblasts, both N- and C-terminal truncations resulted in a weak, additive oncogenic activity. However, not even double truncations caused a v-erbB-like phenotype. Upon EGF-binding, on the other hand, both normal and C-terminally truncated EGFRs resembled v-erbB in their fibroblast transforming potential. In erythroblasts, N-terminal truncation was sufficient to induce constitutive self-renewal, which was enhanced by deletion of 32 C-terminal amino acids but abolished by a larger truncation of 202 amino acids. In contrast to the normal EGFR, the receptor lacking 32 C-terminal amino acids resembled v-erbB in conferring erythropoietin independence for spontaneous differentiation to the transformed erythroblasts. Our results indicate that the C-terminal domain of the EGFR is non-essential in fibroblast transformation, but seems to be crucial for both self renewal induction and specificity of receptor function in erythroblasts.
Khazaie
K
K
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, FRG.
Dull
T J
TJ
Graf
T
T
Schlessinger
J
J
Ullrich
A
A
Beug
H
H
Vennström
B
B
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000209:etiology*; D002478:Cells, Cultured; D002645:Chickens; D004252:DNA Mutational Analysis; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D004900:Erythroblasts; D004921:Erythropoietin / Q000494:pharmacology; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D007942:Leukemia, Experimental / Q000235:genetics; D008938:Mitosis; D009856:Oncogene Proteins, Viral / Q000235:genetics; D011485:Protein Binding; D013329:Structure-Activity Relationship
D009856:Oncogene Proteins, Viral; D004921:Erythropoietin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors