Localization of the insulin receptor-related receptor gene to human chromosome 1

Shier, Peter; Willard, H.F.; Watt, Valerie M.

doi:10.1159/000132963

Cited by 10 publications

(3 citation statements)

References 1 publication

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“…It is unlikely that trkA and IRR are driven by a bi-directional promoter; however, they are co-expressed at the cellular level in both neuronal and non-neuronal tissues in rat (Reinhardt et al, 1994;Tsuji et al, 1996), suggesting that they may share regulatory elements acting both in cis and in trans. Similar genomic arrangements may exist in other species; thus, both the IRR and trkA genes are located in human chromosome 1 (Shier et al, 1990;Valent et al, 1997). We have shown that a small region of 150 nucleotides, 5' to the mouse trkA gene, is required for promoter activity and for cell-type speci®c transcription.…”

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confidence: 61%

Molecular cloning and characterization of the 5′ region of the mouse trkA proto-oncogene

et al. 1999

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The trkA proto-oncogene encodes a high-a nity NGF receptor that is essential for the survival, di erentiation and maintenance of many neural and non-neural cell types. Altered expression of the trkA gene or trkA receptor malfunction have been implicated in neurodegeneration, tumor progression and oncogenesis. We have cloned and characterized the 5' region of the mouse trkA gene and have identi®ed its promoter. trkA promoter sequences are GC-rich, lack genuine TATA or CAAT boxes, and are contained within a CpG island which extends over the entire ®rst coding exon. The mouse trkA transcription start site is located 70/71 bp upstream to the AUG translation initiation codon. Sequence analysis showed that the gene encoding the insulin receptor-related receptor, IRR, is located just 1.6 kbp upstream to the trkA gene and is transcribed in the opposite direction. We have used trkA-CAT transcriptional fusions to study trkA promoter function in transient transfection experiments. RNase protection assays and CAT protein ELISA analyses showed that a 150 bp long DNA segment, immediately upstream to the start site, is su cient to direct accurate transcription in trkA-expressing cells. Dissection of this fragment allowed us to identify a 13 bp cis-regulatory element essential for both promoter activity and cell-type speci®c expression. Deletion of this 13 bp segment as well as modi®cation of its sequence by site-directed mutagenesis led to a dramatic decline in promoter activity. Gel mobility shift assays carried out with double-stranded oligonucleotides containing the 13 bp element revealed several speci®c DNA-protein complexes when nuclear extracts from trkA-expressing cells were used. Supershift experiments showed that the Sp1 transcription factor was a component of one of these complexes. Our results identify a minimal trkA gene promoter, located very close to the transcription start site, and de®ne a 13 bp enhancer within this promoter sequence.

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confidence: 61%

Molecular cloning and characterization of the 5′ region of the mouse trkA proto-oncogene

et al. 1999

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“…Previously, the INSRR locus was localized to chromosome 1 by the use of a human hamster somatic cell panel (Shier et al, 1990). As a first step to assess a possible role of INSRR in heritable forms of diabetes or neurodegenerative disease, we carried out a regional mapping of the human INSRR locus.…”

Section: Rationale and Significancementioning

confidence: 99%

The assignment of the human insulin receptor-related receptor gene (INSRR) to chromosome 1q21→q23 by the use of radiation hybrid mapping

Whitmore¹,

Maurer²,

Day³

et al. 1999

Cytogenet Genome Res

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“…Interestingly, the insulin receptor-related receptor gene has been localized to human chromosome 1, a hot spot for mutations, deletions and rearrangements in human neuroblastoma tumors [14]. Since the presence of endogenous IRR in neuroblastoma tumors as measured by a kinase immunoprecipitation assay seems to be related to the stage of the tumors [5], elucidation of both biological function and natural ligand of the receptor might prove to be important and of clinical relevance in the area of neuroblastoma research.…”

Section: 5%mentioning

confidence: 99%

Cloning and Sequencing of the Complete cDNA Encoding the Human Insulin Receptor Related Receptor

Hänze

Berthold²,

Klammt³

et al. 1999

Horm Metab Res

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The insulin receptor related receptor (IRR) is a heterotetrameric transmembrane receptor with intrinsic tyrosine kinase activity. The IRR shares large homology with the insulin and the insulin-like growth factor-1 (IGF-I) receptor with regard to amino acid sequence and protein structure. So far, only a partial human sequence containing the complete 3' end has been reported, although the full-length human IRR cDNA had been used for transfection studies and functional analysis of the receptor. We have isolated a full-length human IRR cDNA and report on the 5' translated and untranslated region of the human IRR gene. The full length IRR sequence contains 4150 bases and shares a high degree of homology with the guinea pig IRR cDNA sequence and rat IRR sequences that had been reported earlier on by others. Sequencing of the IRR cDNA revealed that the human IRR cDNA contains 341 bases corresponding to the IRR 5' end in addition to the bases that had been reported on before. Also, this sequence contains the start codon of translation. The full length cDNA for the human IRR can now be used for functional expression studies and to elucidate the nature of the ligand for this receptor type.

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Localization of the insulin receptor-related receptor gene to human chromosome 1

Cited by 10 publications

References 1 publication

Molecular cloning and characterization of the 5′ region of the mouse trkA proto-oncogene

Molecular cloning and characterization of the 5′ region of the mouse trkA proto-oncogene

The assignment of the human insulin receptor-related receptor gene (INSRR) to chromosome 1q21→q23 by the use of radiation hybrid mapping

Cloning and Sequencing of the Complete cDNA Encoding the Human Insulin Receptor Related Receptor

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