Disease relevance of INSRR

• RESULTS: IRR mRNA expression was found in 25 (51%) neuroblastomas and correlated with stages 1, 2, 3, and 4S disease and with age </=12 months at diagnosis [1].
• In addition, the IRR mRNA was expressed in rhabdomyosarcoma, in leiomyosarcoma, in one of the Ewing sarcoma and in the neurofibrosarcoma cell line [2].
• IRR gene expression diminishes in the majority of sensory neurons postnatally, but remains abundant in a subpopulation of adult rat trigeminal and dorsal root ganglion neurons [3].
• CONCLUSIONS: There was no difference in IR receptor expression and IR autophosphorylation between normal myometrium and leiomyoma [4].
• We found a slightly lower risk of breast cancer among women ever having had a multiple birth than among women with singletons only (IRR = 0.89, 95% CI = 0.73-1.09) [5].

Psychiatry related information on INSRR

• Having an incontinent wife put men at greater risk for depressive symptoms (unadj. IRR = 1.13, 95% CIs = 1.02, 1.25), although this relation became nonsignificant with the addition of control variables [6].
• MLU for IRR speech was greater than that for productive utterances, which supports the idea that these productions facilitate language development [7].

High impact information on INSRR

• IS911 transposition occurs in several steps: synapsis of the two transposon ends (IRR and IRL); formation of a figure-of-eight intermediate where both ends are joined by a single-strand bridge; resolution into a circular form carrying an IRR-IRL junction; and insertion into a DNA target [8].
• The C-terminal domain of IRRR was found to abolish binding in IR and IGFIR context, whereas other constructs bound ligands [9].
• Increased tyrosine phosphorylation of these proteins is also observed in cells expressing a transforming chicken c-Src (mutant Phe-527) and in cells with the activated tyrosine kinase domains of the Drosophila insulin receptor, human insulin-like growth factor I receptor, and human insulin receptor-related receptor [10].
• Characterization of the endogenous insulin receptor-related receptor in neuroblastomas [11].
• The intrinsic tyrosine kinase activity of this endogenous IRR was activated by the agonist monoclonal antibody to IRR but not by nerve growth factor, insulin-like growth factor I, or insulin [11].

Chemical compound and disease context of INSRR

• Folate intake was inversely associated with colorectal cancer risk (IRR = 0.6, 95% CI = 0.4-1.1, p for trend = 0.25) [12].
• INSRR coding for the insulin receptor-related receptor (IRR) is located within the 1q21-q23 region linked with type-2 diabetes mellitus in Pima Indians and Caucasians [13].

Biological context of INSRR

• The assignment of the human insulin receptor-related receptor gene (INSRR) to chromosome 1q21-->q23 by the use of radiation hybrid mapping [14].
• IRR mRNA expression also correlated with an undifferentiated histology but not with the proliferation rate [1].
• Coexpression of insulin receptor-related receptor and insulin-like growth factor 1 receptor correlates with enhanced apoptosis and dedifferentiation in human neuroblastomas [1].
• Replacement of the kinase domain of the IGF-IR or its C-terminal lobe alone into the IRR caused a complete restoration of the tyrosine phosphorylation of the IRR [15].
• We have cloned a full-length cDNA encoding the human IRR by screening a human kidney cDNA library [16].

Anatomical context of INSRR

• In all of the seven neuroblastoma cell lines and in five of the 11 STS cell lines, the IRR mRNA was detected [2].
• Since tyrosine kinase receptors, including the IGF-I-R, may be involved in tumor genesis, we examined the expression of IRR mRNA and IGF-I-mRNA in 18 tumor cell lines using RT-PCR and the solution hybridization/RNAse protection assay [2].
• In the present studies we report Northern blot analyses and polymerase chain reaction data, which indicate that the IRR mRNA is expressed in a variety of tissues, including the human kidney, heart, skeletal muscle, liver, and pancreas [17].
• We expressed the IRR cDNA lacking the 24-base pair insert in NIH-3T3 cells to study the biosynthesis, tyrosine phosphorylation, and ligand binding properties of the IRR [16].
• However, Chinese hamster ovary (CHO) cells stably overexpressing the kinase domain of IRR exhibited elevated basal thymidine incorporation and 2-deoxyglucose uptake compared with CHO cells and CHO cells overexpressing wild-type IR [17].

Associations of INSRR with chemical compounds

• Our data suggest an influence of IRR on IGF signaling via IGF-1R because coexpression of these two receptor tyrosine kinases was significantly correlated with an undifferentiated histology, a high AI, and an advanced survival probability [1].
• Phosphotyrosine detection revealed a lack in the constitutive activation of the IRR described for analogous constructs of the two other members of the family [15].
• We conclude that INSRR has no detectable mutations contributing to diabetes in the Pima Indians [13].
• Binding properties of chimeric insulin receptors containing the cysteine-rich domain of either the insulin-like growth factor I receptor or the insulin receptor related receptor [18].
• Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary [19].

Regulatory relationships of INSRR

• Furthermore, IRR mRNA was found only in cell lines that also expressed IGF-I-R mRNA [2].

Other interactions of INSRR

• CONCLUSION: IRR expression is a new marker for a favorable prognosis in neuroblastoma that is independent of MYCN amplification and age at diagnosis [1].
• In particular, the mRNA levels of IRR and IGF-I-R were compared by semi-quantitative RT-PCR in seven neuroblastomas and 11 soft tissue sarcomas (STS), five of which were of neuronal origin [2].
• We amplified human kidney IRR by the polymerase chain reaction to quantitate the proportion of transcripts which included the 24-nucleotide sequence between exons 13 and 14 [16].
• In contrast, chimeric receptors containing exon 3 of IRR did not bind either IGF-I, IGF-II, or relaxin [18].

Analytical, diagnostic and therapeutic context of INSRR

• In the present work, we investigated the potential of the third member of the family, insulin receptor-related receptor (IRR), to associate with known interaction partners of the InsR and the IGF-I receptor in a yeast two-hybrid assay [15].
• In situ hybridization histochemical analysis revealed that IRR transcripts were present in a subpopulation of cells within distal tubules of human kidney, beyond the most proximal segment of the distal convoluted tubule [20].
• An extensive molecular search using several approaches, including the screening of cDNA libraries and PCR amplification with degenerate primers, did not yield an IRR ligand [19].
• In women with Quetelet's index equal to or greater than 24 there was a positive relation between coffee intake and breast cancer risk (chi 2 trend = 2.33, P = 0.13), where the corresponding age-adjusted IRR was 2.1 (95% confidence intervals, 0.8 and 5.2) [21].
• RESULTS: In the cohort analyses, risk of depression was significantly higher in men with BPH compared to those without (IRR 2.17, 2.12-2.22), but was not significantly different for men exposed to alpha 1-blockers versus those unexposed when adjusted for the presence of BPH [22].

References