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Gene Review

InR  -  Insulin-like receptor

Drosophila melanogaster

Synonyms: 18402, CG18402, DIHR, DILR, DIR, ...
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Psychiatry related information on InR


High impact information on InR

  • In a screen for patterning mutants, we isolated alleles of tsc1, a component of the insulin receptor (InR) growth control pathway [2].
  • These age-related changes are minimized or absent in long-lived flies when systemic levels of insulin-like peptides are reduced and by mutations of the only receptor, InR, or its substrate, chico [3].
  • Moreover, interfering with InR signaling exclusively in the heart, by overexpressing the phosphatase dPTEN or the forkhead transcription factor dFOXO, prevents the decline in cardiac performance with age [3].
  • Examples include the related tyrosine kinase receptors InR (Drosophila melanogaster) and DAF-2 (Caenorhabditis elegans) that are homologues of the mammalian insulin-like growth factor type 1 receptor (IGF-1R) [4].
  • We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality [5].

Biological context of InR

  • Overexpression of INR beta-Myc and betaDelta kinases conferred an equivalent increase in cell proliferation in both 293 and Madin-Darby canine kidney cells, indicating that this growth response is independent of the carboxyl-terminal extension [6].
  • However, INR beta-Myc-expressing cells exhibited enhanced survival relative to parental and betaDelta cells, suggesting that the carboxyl-terminal extension, through its interaction with IRS-1, plays a role in the regulation of cell death [6].
  • RESULTS: We demonstrate that varying the activity of the Drosophila insulin receptor homolog (DInr) during development regulates organ size by changing cell size and cell number in a cell-autonomous manner [7].
  • We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue [5].
  • The core promoter lacks a TATA box and is composed of an initiator element (InR) and a downstream promoter element (DPE), a combination found primarily in Drosophila gene promoters and rarely observed in mammalian gene promoters [8].

Anatomical context of InR


Associations of InR with chemical compounds

  • The Drosophila insulin receptor (INR) homolog includes an extension of approximately 400 amino acids at the carboxyl-terminal end of its beta subunit containing several tyrosine-based motifs known to mediate interactions with signaling proteins [6].
  • The identity of this immunoreactivity as a dInsR was confirmed by two additional schemes, in vivo binding of labeled insulin and immunolocalization of phosphotyrosine [12].
  • Similarly to the InR, HMGCR is expressed in the corpus allatum (ca), which is the gland where JH biosynthesis occurs [13].
  • The ability of low concentrations of DTT to deactivate the DIR kinase suggests that, like the mammalian receptor, beta-subunit thiols may be involved in regulation of conformational changes between activated and unactivated receptor states [14].
  • The pattern of lectin binding indicates that glycosylation of the DIR and rat insulin receptors differs, with the DIR containing primarily high mannose-type oligosaccharides [14].

Physical interactions of InR

  • The INR proreceptor (M(r) 280 kDa) is processed proteolytically to generate an insulin-binding alpha subunit (M(r) 120 kDa) and a beta subunit (M(r) 170 kDa) with protein tyrosine kinase domain [15].

Other interactions of InR

  • DInR functions as a guidance receptor for the adapter protein Dock/Nck [16].
  • Sequences encoding the InR, DPE, AP-2, and Sp1 sites were 100% conserved between human and murine KCC1 genes [8].
  • The INR beta 170 subunit contains a novel domain at the carboxyterminal side of the tyrosine kinase, in the form of a 60 kDa extension which contains multiple potential tyrosine autophosphorylation sites [15].
  • These transporters genetically interact with TOR and other InR signalling components, indicating that they control growth by directly or indirectly modulating the effects of TOR signalling [17].

Analytical, diagnostic and therapeutic context of InR

  • Adults from yeast-deprived larvae phenocopied many traits of InR and chico mutants: small body size, delayed eclosion, reduced ovariole number and reduced age-specific fecundity [18].


  1. Disruption of insulin pathways alters trehalose level and abolishes sexual dimorphism in locomotor activity in Drosophila. Belgacem, Y.H., Martin, J.R. J. Neurobiol. (2006) [Pubmed]
  2. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Bateman, J.M., McNeill, H. Cell (2004) [Pubmed]
  3. Insulin regulation of heart function in aging fruit flies. Wessells, R.J., Fitzgerald, E., Cypser, J.R., Tatar, M., Bodmer, R. Nat. Genet. (2004) [Pubmed]
  4. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P.C., Cervera, P., Le Bouc, Y. Nature (2003) [Pubmed]
  5. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Tatar, M., Kopelman, A., Epstein, D., Tu, M.P., Yin, C.M., Garofalo, R.S. Science (2001) [Pubmed]
  6. The carboxyl terminal extension of the Drosophila insulin receptor homologue binds IRS-1 and influences cell survival. Marin-Hincapie, M., Garofalo, R.S. J. Biol. Chem. (1999) [Pubmed]
  7. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Brogiolo, W., Stocker, H., Ikeya, T., Rintelen, F., Fernandez, R., Hafen, E. Curr. Biol. (2001) [Pubmed]
  8. Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element. Zhou, G.P., Wong, C., Su, R., Crable, S.C., Anderson, K.P., Gallagher, P.G. Blood (2004) [Pubmed]
  9. Mutations in insulin signaling pathway alter juvenile hormone synthesis in Drosophila melanogaster. Tu, M.P., Yin, C.M., Tatar, M. Gen. Comp. Endocrinol. (2005) [Pubmed]
  10. IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback. Marr, M.T., D'Alessio, J.A., Puig, O., Tjian, R. Genes Dev. (2007) [Pubmed]
  11. Tissue localization of Drosophila melanogaster insulin receptor transcripts during development. Garofalo, R.S., Rosen, O.M. Mol. Cell. Biol. (1988) [Pubmed]
  12. Insulin-like receptor and insulin-like peptide are localized at neuromuscular junctions in Drosophila. Gorczyca, M., Augart, C., Budnik, V. J. Neurosci. (1993) [Pubmed]
  13. Hmgcr in the Corpus Allatum Controls Sexual Dimorphism of Locomotor Activity and Body Size via the Insulin Pathway in Drosophila. Belgacem, Y.H., Martin, J.R. PLoS ONE (2007) [Pubmed]
  14. Drosophila insulin receptor: lectin-binding properties and a role for oxidation-reduction of receptor thiols in activation. Marin-Hincapie, M., Garofalo, R.S. Endocrinology (1995) [Pubmed]
  15. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. Fernandez, R., Tabarini, D., Azpiazu, N., Frasch, M., Schlessinger, J. EMBO J. (1995) [Pubmed]
  16. Axons guided by insulin receptor in Drosophila visual system. Song, J., Wu, L., Chen, Z., Kohanski, R.A., Pick, L. Science (2003) [Pubmed]
  17. PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Goberdhan, D.C., Meredith, D., Boyd, C.A., Wilson, C. Development (2005) [Pubmed]
  18. Juvenile diet restriction and the aging and reproduction of adult Drosophila melanogaster. Tu, M.P., Tatar, M. Aging Cell (2003) [Pubmed]
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