A 1.8 kb alternative transcript from the human epidermal growth factor receptor gene encodes a truncated form of the receptor.
The epidermal growth factor receptor (EGFR) is encoded by the c-erbB1 proto-oncogene and plays an important role in the control of cell growth and differentiation. To study the potential growth regulatory role of soluble EGF receptors, we have isolated cDNA clones encoding a truncated, secreted form of the human EGFR. The 5' sequence of this cDNA is identical to the EGFR transcript encoding the full-length receptor through exon 10. The unique 3' sequence encodes two additional amino acid residues before encountering an in-frame stop codon, a poly(A) addition site and a poly(A)+ tail. Sequence comparison with genomic DNA sequences demonstrates that this alternative transcript arises by read-through of a splice donor site. As a result, this transcript encodes a portion of the extracellular ligand-binding domain, but lacks the transmembrane domain and the intracellular tyrosine kinase catalytic domain present in the EGFR. Conditioned medium from transfected fibroblast cells contains a 60 kDa protein that is specifically immunoprecipitated by an EGFR monoclonal antibody. These findings demonstrate that alternative processing of the human EGFR transcript produces a secreted product composed of only the extracellular ligand-binding domain.
Reiter
J L
JL
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Maihle
N J
NJ
D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D015342:DNA Probes; D066246:ErbB Receptors / Q000737:chemistry* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009857:Oncogenes / Q000235:genetics; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000235:genetics; D016415:Sequence Alignment; D017421:Sequence Analysis; D017384:Sequence Deletion / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
D015342:DNA Probes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D066246:ErbB Receptors