title: Truncation of the human EGF receptor leads to differential transforming potentials in primary avian fibroblasts and erythroblasts.
abstract: 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.
authors.affiliation: Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, FRG.
authors.forename: K
authors.initials: K
authors.lastname: Khazaie
authors.forename: T J
authors.initials: TJ
authors.lastname: Dull
authors.forename: T
authors.initials: T
authors.lastname: Graf
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
authors.forename: H
authors.initials: H
authors.lastname: Beug
authors.forename: B
authors.initials: B
authors.lastname: Vennström
mesh_terms: 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
chemical_list: D009856:Oncogene Proteins, Viral; D004921:Erythropoietin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors