title: Conservation of RET proto-oncogene splicing variants and implications for RET isoform function.
abstract: The RET proto-oncogene encodes a receptor tyrosine kinase required for development of the kidney and neural crest-derived cell types. Alternative splicing of the 3' exons of human RET results in three protein isoforms with distinct C-termini: RET9, RET51, and RET43. These RET isoforms show differential binding to downstream adapter molecules, suggesting they may have distinct signaling functions. We have characterized Ret 3' sequences in mouse and investigated alternative splicing of this region. We found that the organization of Ret 3' sequences is very similar to human RET. The mouse locus also has alternatively spliced C-terminal coding regions, and the sequences corresponding to RET9 and RET51 are highly conserved in both position and sequence with the human locus. Further, we compared the predicted C-terminal amino acids of RET9 and RET51 in seven vertebrate species, and found that they are well conserved. We have identified sequence encoding a putative ret43 isoform in mouse, however the predicted amino acid sequence showed low homology to human RET43. Our data suggest that RET isoforms are evolutionarily highly conserved over a broad range of species, which may indicate that each isoform has a distinct role in normal RET function.
authors.affiliation: Department of Pathology, Queen's University, Kingston, ON, Canada.
authors.forename: M T
authors.initials: MT
authors.lastname: Carter
authors.forename: J L
authors.initials: JL
authors.lastname: Yome
authors.forename: M N
authors.initials: MN
authors.lastname: Marcil
authors.forename: C A
authors.initials: CA
authors.lastname: Martin
authors.forename: J B
authors.initials: JB
authors.lastname: Vanhorne
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D029721:Drosophila Proteins; D051379:Mice; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse