A complete description of the EGF-receptor exon structure: Implication in oncogenic activation and domain evolution

Thomas Callaghan, Michael Antczak, Tom Flickinger, Maribeth Raines, Mike Myers, Hsing Jien Kung

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In this paper, we report that the chicken Epidermal Growth Factor Receptor (EGF-R), encoded by the proto-oncogene c-erbB, is comprised of 28 exons and spans over 75 Kb. The four previously identified domains which make up the extracellular ligand binding region of the receptor are coded for by two copies of a 300 amino acid repeat. We have demonstrated that the 3′ end of each repeat coincides with the 3′ end of the last exon making up the repeat. This alignment suggests that an exon-duplication may have occurred in the ligand-binding region of the gene. The transmembrane domain is encoded within a single exon and the exon boundaries of the catalytic domain closely match those defined by structural homology with other kinases. Along with the 54 chicken splice sites, the region 5′ to the first exon was also sequenced. The proposed promoter region is greater than 70% GC, contains five repeats of the consensus Sp1 binding sequence and does not have a CCATT or TATA box. In addition to the presence of these characteristic housekeeping features, expression analysis confirms the promoter activity of this region and four sets of TCC repeats similar to those found in the human EGF-R promoter have been identified. To our knowledge this represents the first complete description of the exonintron structure of the EGF-receptor family. The elucidation of the EGF-R exon structure provides insight into the domain evolution of the receptor-kinases and the mechanisms for the oncogenic conversion of EGF-R in erythroleukemias and glioblastomas.

Original languageEnglish
Pages (from-to)2939-2948
Number of pages10
JournalOncogene
Volume8
Issue number11
Publication statusPublished - Nov 1 1993
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Exons
Genetic Promoter Regions
Chickens
Phosphotransferases
Ligands
Housekeeping
Leukemia, Erythroblastic, Acute
TATA Box
RNA Splice Sites
Proto-Oncogenes
Glioblastoma
Catalytic Domain
Amino Acids
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Callaghan, T., Antczak, M., Flickinger, T., Raines, M., Myers, M., & Kung, H. J. (1993). A complete description of the EGF-receptor exon structure: Implication in oncogenic activation and domain evolution. Oncogene, 8(11), 2939-2948.

A complete description of the EGF-receptor exon structure : Implication in oncogenic activation and domain evolution. / Callaghan, Thomas; Antczak, Michael; Flickinger, Tom; Raines, Maribeth; Myers, Mike; Kung, Hsing Jien.

In: Oncogene, Vol. 8, No. 11, 01.11.1993, p. 2939-2948.

Research output: Contribution to journalArticle

Callaghan, T, Antczak, M, Flickinger, T, Raines, M, Myers, M & Kung, HJ 1993, 'A complete description of the EGF-receptor exon structure: Implication in oncogenic activation and domain evolution', Oncogene, vol. 8, no. 11, pp. 2939-2948.
Callaghan T, Antczak M, Flickinger T, Raines M, Myers M, Kung HJ. A complete description of the EGF-receptor exon structure: Implication in oncogenic activation and domain evolution. Oncogene. 1993 Nov 1;8(11):2939-2948.
Callaghan, Thomas ; Antczak, Michael ; Flickinger, Tom ; Raines, Maribeth ; Myers, Mike ; Kung, Hsing Jien. / A complete description of the EGF-receptor exon structure : Implication in oncogenic activation and domain evolution. In: Oncogene. 1993 ; Vol. 8, No. 11. pp. 2939-2948.
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