Proceedings of the National Academy of Sciences · 1989 · 357 citations · 25 references
MedicineMolecular BiologyMolecular GeneticsGene ExpressionGene StructureTranscriptionCore Promoter ElementsExon StructureExon-intron OrganizationPromoter ArchitectureTranscription InitiationTranscription Start SitesExon OrganizationExon-intron BoundariesGene Promoter RegulationInsulin ReceptorsPromoter Activity AnalysisPromoter Region IdentificationTranscriptional InitiationTranscriptional Start Sites
The human insulin receptor gene, INSR, and its promoter region have been isolated and characterized. The gene spans greater than 120 kilobase pairs (kbp) and has 22 exons. All introns interrupt protein coding regions of the gene. The 11 exons encoding the alpha subunit of the receptor are dispersed over greater than 90 kbp, whereas the 11 exons encoding the beta subunit are located together in a region of approximately 30 kbp. Three transcriptional initiation sites have been identified and are located 276, 282, and 283 bp upstream of the translation initiation site. In addition, a 247-bp fragment from the promoter region possessing 62.6% of the maximal promoter activity has been identified. This promoter-active fragment lacks a TATA-like sequence but has two possible binding regions for the transcriptional factor Sp1. Comparison of the exon structure of the tyrosine kinase domain of the INSR with the corresponding regions of the human SRC, ROS, and ERBB2 (NGL) protooncogenes indicates that the exon-intron organization of this region has not been well conserved.
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Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes
A Ullrich, Jeffrey R. Bell, E. Y. Chen et al. · Nature · 1985 · 2.3K citations