Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms.
This study presents the annotated genomic sequence and exon-intron organization of the human and mouse epidermal growth factor receptor (EGFR) genes located on chromosomes 7p11.2 and 11, respectively. We report that the EGFR gene spans nearly 200 kb and that the full-length 170-kDa EGFR is encoded by 28 exons. In addition, we have identified two human and two mouse alternative EGFR transcripts of 2.4-3.0 kb using both computational and experimental methods. The human 3.0-kb and mouse 2.8-kb EGFR mRNAs are predominantly expressed in placenta and liver, respectively, and both transcripts encode 110-kDa truncated receptor isoforms containing only the extracellular ligand-binding domain. We also have demonstrated that the aberrant 2.8-kb EGFR transcript produced by the human A431 carcinoma cell line is generated by splicing to a recombinant 3'-terminal exon located in EGFR intron 16, which apparently was formed as a result of a chromosomal translocation. Finally, we have shown that the human, mouse, rat, and chicken 1.8- to 3.0-kb alternative EGFR transcripts are generated by distinct splicing mechanisms and that each of these mRNAs contains unique 3' sequences that are not evolutionarily conserved. The presence of truncated receptor isoforms in diverse species suggests that these proteins may have important functional roles in regulating EGFR activity.
Reiter
J L
JL
Tumor Biology Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Threadgill
D W
DW
Eley
G D
GD
Strunk
K E
KE
Danielsen
A J
AJ
Sinclair
C S
CS
Pearsall
R S
RS
Green
P J
PJ
Yee
D
D
Lampland
A L
AL
Balasubramaniam
S
S
Crossley
T D
TD
Magnuson
T R
TR
James
C D
CD
Maihle
N J
NJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D020224:Expressed Sequence Tags; D015723:Gene Library; D016678:Genome; D006801:Humans; D007438:Introns; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D008024:Ligands; D020033:Protein Isoforms; D012333:RNA, Messenger; D066246:ErbB Receptors