Gene Symbol: Igf2r
Description: insulin-like growth factor 2 receptor
Alias: IGF-IIR, Igfr2, cation-independent mannose-6-phosphate receptor
Species: rat
Products:     Igf2r

Top Publications

  1. De Souza A, Hankins G, Washington M, Orton T, Jirtle R. M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet. 1995;11:447-9 pubmed
    The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) functions in the intracellular trafficking of lysosomal enzymes, the activation of the potent growth inhibitor, transforming growth factor beta 2, and the ..
  2. Lee S, Nathans D. Proliferin secreted by cultured cells binds to mannose 6-phosphate receptors. J Biol Chem. 1988;263:3521-7 pubmed
  3. de la Monte S, Tong M, Bowling N, Moskal P. si-RNA inhibition of brain insulin or insulin-like growth factor receptors causes developmental cerebellar abnormalities: relevance to fetal alcohol spectrum disorder. Mol Brain. 2011;4:13 pubmed publisher
    ..Potential therapeutic strategies to reduce the long-term impact of prenatal alcohol exposure may include treatment with agents that restore brain insulin and IGF responsiveness. ..
  4. Ruttenstock E, Doi T, Dingemann J, Puri P. Prenatal administration of retinoic acid upregulates insulin-like growth factor receptors in the nitrofen-induced hypoplastic lung. Birth Defects Res B Dev Reprod Toxicol. 2011;92:148-51 pubmed publisher
    ..Upregulation of pulmonary gene and protein expression of IGFRs after prenatal RA treatment in the nitrofen model suggests that RA may promote lung growth by stimulating IGFRs mediated alveologenesis. ..
  5. Zakaria R, Rajikin M, Yaacob N, Nor N. Immunolocalization of insulin-like growth factors and their receptors in the diabetic mouse oviduct and uterine tissues during the preimplantation period. Acta Histochem. 2009;111:52-60 pubmed publisher
    ..In conclusion, the oviductal immunolabelling for IGFs and their receptors was significantly altered by maternal diabetes, which may be of importance in the pathogenesis of preimplantation diabetic embryopathy. ..
  6. McCann J, Xu Y, Frechette R, Guazzarotti L, Polychronakos C. The insulin-like growth factor-II receptor gene is associated with type 1 diabetes: evidence of a maternal effect. J Clin Endocrinol Metab. 2004;89:5700-6 pubmed
    ..IGF-II receptor (IGF2R), the best-studied imprinted gene in the IDDM8 region, encodes the IGF-2 receptor, a protein involved in many ..
  7. Kang J, Bell J, Leaf A, Beard R, Chandraratna R. Retinoic acid alters the intracellular trafficking of the mannose-6-phosphate/insulin-like growth factor II receptor and lysosomal enzymes. Proc Natl Acad Sci U S A. 1998;95:13687-91 pubmed
    ..we showed that retinoic acid (RA) binds to the mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) with high affinity, suggesting that M6P/IGF2R may be a receptor for RA...
  8. Puxbaum V, Nimmerfall E, Bäuerl C, Taub N, Blaas P, Wieser J, et al. M6P/IGF2R modulates the invasiveness of liver cells via its capacity to bind mannose 6-phosphate residues. J Hepatol. 2012;57:337-43 pubmed publisher
    The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R), a multifunctional protein, plays a central role in intracellular targeting of lysosomal enzymes and control of insulin-like growth factor II (IGF-II) bioactivity...
  9. Jofré G, Balmaceda V, Sartor T, Carvelli L, Barrera P, Sosa M. Organ-specific changes in the expression of mannose-6-phosphate receptors during postnatal development in rats. Cells Tissues Organs. 2009;190:27-33 pubmed publisher
    ..We propose that in the pancreas, both receptors may be involved in increasing the proteolytic activity of this exocrine gland during postnatal development. ..

More Information


  1. Tsujiuchi T, Sasaki Y, Tsutsumi M, Konishi Y. Alterations of the M6p/Igf2 receptor gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. Mol Carcinog. 2003;36:32-7 pubmed
    ..and total RNAs were extracted from each for assessment of mutations and levels of aberrant transcripts of the M6p/Igf2r gene by reverse transcription (RT)-polymerase chain reaction (PCR) single-strand conformation polymorphism ..
  2. Lee F, Peng S, Lin K, Chen R, Ho T, Tsai F, et al. HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy. J Cell Physiol. 2018;233:979-989 pubmed publisher
    ..HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. ..
  3. Kreiling J, Montgomery M, Wheeler J, Kopanic J, Connelly C, Zavorka M, et al. Dominant-negative effect of truncated mannose 6-phosphate/insulin-like growth factor II receptor species in cancer. FEBS J. 2012;279:2695-713 pubmed publisher
    Oligomerization of the mannose 6-phosphate/insulin-like growth factor?II receptor (M6P/IGF2R) is important for optimal ligand binding and internalization...
  4. Belmonte S, Romano P, Fornés W, Sosa M. Changes in distribution of phosphomannosyl receptors during maturation of rat spermatozoa. Biol Reprod. 2000;63:1172-8 pubmed
    ..Receptors were localized on the plasmalemma of spermatozoa, as observed by immunoelectron microscopy. Changes in distribution may be related to a maturation process, which suggests new roles for the phosphomannosyl receptors. ..
  5. Progida C, Malerød L, Stuffers S, Brech A, Bucci C, Stenmark H. RILP is required for the proper morphology and function of late endosomes. J Cell Sci. 2007;120:3729-37 pubmed
    ..We propose that RILP might coordinate the biogenesis of MVEs with dynein-mediated motility. ..
  6. Villuendas G, Botella Carretero J, Lopez Bermejo A, Gubern C, Ricart W, Fernandez Real J, et al. The ACAA-insertion/deletion polymorphism at the 3' UTR of the IGF-II receptor gene is associated with type 2 diabetes and surrogate markers of insulin resistance. Eur J Endocrinol. 2006;155:331-6 pubmed
    ..The ACAA-insertion/deletion polymorphism at the 3' UTR of IGFIIR is associated with type 2 diabetes and influences surrogate markers of insulin resistance in non-diabetic subjects. ..
  7. Lee S, Chu C, Huang E, Lu M, Liu J, Liu C, et al. Roles of insulin-like growth factor II in cardiomyoblast apoptosis and in hypertensive rat heart with abdominal aorta ligation. Am J Physiol Endocrinol Metab. 2006;291:E306-14 pubmed
    ..The increased cardiac IGF-II, IGF-IIR, caspase 9, and cellular apoptosis were also found in hypertensive rats with abdominal aorta ligation...
  8. Hawkes C, Jhamandas J, Harris K, Fu W, MacDonald R, Kar S. Single transmembrane domain insulin-like growth factor-II/mannose-6-phosphate receptor regulates central cholinergic function by activating a G-protein-sensitive, protein kinase C-dependent pathway. J Neurosci. 2006;26:585-96 pubmed
  9. Xu Y, Grundy P, Polychronakos C. Aberrant imprinting of the insulin-like growth factor II receptor gene in Wilms' tumor. Oncogene. 1997;14:1041-6 pubmed
    ..The IGF2R gene encodes a nonmitogenic receptor which targets IGF-II to the lysosomes for degradation and, therefore, ..
  10. Thesleff I. Craniofacial developmental biology--an expanding field of dental research. Proc Finn Dent Soc. 1992;88:163-8 pubmed
  11. Chu C, Huang C, Lu M, Lin J, Tsai F, Tsai C, et al. Enhancement of AG1024-induced H9c2 cardiomyoblast cell apoptosis via the interaction of IGF2R with Galpha proteins and its downstream PKA and PLC-beta modulators by IGF-II. Chin J Physiol. 2009;52:31-7 pubmed
    ..and that apoptosis is required for upregulating the IGF-II and the IGF-II/ mannose 6-phosphate receptor (IGF2R) gene. However, the role of IGF-II in the regulation of cell apoptosis through IGF2R is little known...
  12. Sheng J, Organ E, Hao C, Wells K, Ruley H, Rubin D. Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection. BMC Cell Biol. 2004;5:32 pubmed
    ..type 1 involved the insulin growth factor-2 (IGF-II) pathway, including: the mannose-6-phosphate/IGF2 receptor (Igf2r), a protease associated with insulin growth factor binding protein 5 (Prss11), and the CTCF transcriptional ..
  13. Pai P, Kuo C, Ho T, Lin J, Lin D, Tsai F, et al. p53-mediated miR-18 repression activates HSF2 for IGF-IIR-dependent myocyte hypertrophy in hypertension-induced heart failure. Cell Death Dis. 2017;8:e2990 pubmed publisher
  14. McCusker R, Novakofski J. Zinc partitions insulin-like growth factors (IGFs) from soluble IGF binding protein (IGFBP)-5 to the cell surface receptors of BC3H-1 muscle cells. J Cell Physiol. 2003;197:388-99 pubmed
    ..Zn(2+) was active at physiological doses depressing IGF binding to IGFBP-5 and the IGF-2R at 15-20 microM. Hence, a novel mechanism is further characterized by which the trace micronutrient Zn(2+) could regulate IGF activity. ..
  15. Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, et al. Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A. 2000;97:8439-44 pubmed
  16. Hirosako K, Imasato H, Hirota Y, Kuronita T, Masuyama N, Nishioka M, et al. 3-Methyladenine specifically inhibits retrograde transport of cation-independent mannose 6-phosphate/insulin-like growth factor II receptor from the early endosome to the TGN. Biochem Biophys Res Commun. 2004;316:845-52 pubmed
    ..The results suggest that the effect of 3-MA is restricted to the retrieval of MPR300 from early/recycling endosomes. ..
  17. Romano P, López A, Mariani M, Sartor T, Belmonte S, Sosa M. Expression and binding properties of the two mannose-6-phosphate receptors differ during perinatal development in rat liver. Biochem Biophys Res Commun. 2002;295:1000-6 pubmed
    ..These results demonstrate that both receptors change differentially during perinatal development, suggesting that they play distinct roles during organ maturation. ..
  18. Tsujiuchi T, Sasaki Y, Oka Y, Kuniyasu H, Konishi Y, Tsutsumi M. Alterations of the M6p/Igf2 receptor gene in hepatocellular carcinomas induced by N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet in rats. Mol Carcinog. 2004;39:199-205 pubmed
    To elucidate whether the M6p/Igf2 receptor (M6p/Igf2r) gene might be involved in exogenous and endogenous liver carcinogenesis, we investigated its alteration in hepatocellular carcinomas (HCCs) induced by N-nitrosodiethylamine (DEN) and ..
  19. Kang J, Bell J, Beard R, Chandraratna R. Mannose 6-phosphate/insulin-like growth factor II receptor mediates the growth-inhibitory effects of retinoids. Cell Growth Differ. 1999;10:591-600 pubmed
    Both retinoids and the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) have been shown to play an important role in controlling cell growth during embryonic development and oncogenesis. Our recent work (Kang et al...
  20. MacDonald R, Pfeffer S, Coussens L, Tepper M, Brocklebank C, Mole J, et al. A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. Science. 1988;239:1134-7 pubmed
    ..These results indicate that the type II IGF receptor contains cooperative, high-affinity binding sites for both IGF-II and Man-6-P-containing proteins. ..
  21. Martín Montañez E, Pavía J, Santin L, Boraldi F, Estivill Torrus G, Aguirre J, et al. Involvement of IGF-II receptors in the antioxidant and neuroprotective effects of IGF-II on adult cortical neuronal cultures. Biochim Biophys Acta. 2014;1842:1041-51 pubmed publisher
    ..In this study, we demonstrated that the antioxidant effect of IGF-II is at least partially mediated by IGF-II receptors. ..
  22. Dagvajantsan B, Aoki M, Warita H, Suzuki N, Itoyama Y. Up-regulation of insulin-like growth factor-II receptor in reactive astrocytes in the spinal cord of amyotrophic lateral sclerosis transgenic rats. Tohoku J Exp Med. 2008;214:303-10 pubmed
    ..We suggest that IGF receptors may play a key role in the pathogenesis, and may have therapeutic implications in ALS. ..
  23. Weng Y, Kuo W, Lin Y, Kuo C, Tzang B, Tsai F, et al. Danshen mediates through estrogen receptors to activate Akt and inhibit apoptosis effect of Leu27IGF-II-induced IGF-II receptor signaling activation in cardiomyoblasts. Food Chem Toxicol. 2013;56:28-39 pubmed publisher
    ..All our data indicated that Danshen exerts strong estrogenic activity which can be considered a novel selective estrogen receptor modulator (SERM) against IGF2R signaling that blocks cardiac apoptosis.
  24. Pantaleon M, Jericho H, Rabnott G, Kaye P. The role of insulin-like growth factor II and its receptor in mouse preimplantation development. Reprod Fertil Dev. 2003;15:37-45 pubmed
    ..These responses indicate that the IGF-II/M6P receptor is functional and likely to participate in such a regulatory circuit. The functional role of IGF-II and its receptor is discussed with reference to regulation of early development. ..
  25. Lin K, Kuo C, Kuo W, Ho T, Pai P, Chen W, et al. NFIL3 suppresses hypoxia-induced apoptotic cell death by targeting the insulin-like growth factor 2 receptor. J Cell Biochem. 2015;116:1113-20 pubmed publisher
    The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF2R) over-expression correlates with heart disease progression...
  26. Saris J, Derkx F, de Bruin R, Dekkers D, Lamers J, Saxena P, et al. High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin. Am J Physiol Heart Circ Physiol. 2001;280:H1706-15 pubmed
    ..Binding precedes internalization and proteolytic activation to renin thereby supporting the concept of cardiac angiotensin formation by renal prorenin...
  27. Chu C, Tzang B, Chen L, Liu C, Tsai F, Tsai C, et al. Activation of insulin-like growth factor II receptor induces mitochondrial-dependent apoptosis through G(alpha)q and downstream calcineurin signaling in myocardial cells. Endocrinology. 2009;150:2723-31 pubmed publisher
    ..Suppression of IGF-IIR signaling pathways may be a good strategy for both the protection against myocardial cell apoptosis and the prevention of heart failure progression. ..
  28. Nguyen G. Renin/prorenin receptors. Kidney Int. 2006;69:1503-6 pubmed
  29. Chu C, Lo J, Hu W, Lu R, Chang M, Tsai F, et al. Histone acetylation is essential for ANG-II-induced IGF-IIR gene expression in H9c2 cardiomyoblast cells and pathologically hypertensive rat heart. J Cell Physiol. 2012;227:259-68 pubmed publisher
    ..Taken together, this study demonstrates that histone acetylation plays a critical role in IGF-IIR up-regulation during pathological cardiac diseases and might provide a targeting gene in transcriptional therapies for the failing heart. ..
  30. Lau M, Stewart C, Liu Z, Bhatt H, Rotwein P, Stewart C. Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. Genes Dev. 1994;8:2953-63 pubmed
    ..that inherit a nonfunctional insulin-like growth factor-II/cation-independent mannose 6-phosphate receptor (Igf2r) gene from their fathers are viable and develop normally into adults...
  31. Chen Y, Lee N, Pai P, Chung L, Shen C, Rajendran P, et al. Tanshinone-induced ERs suppresses IGFII activation to alleviate Ang II-mediated cardiac hypertrophy. J Recept Signal Transduct Res. 2017;37:493-499 pubmed publisher
    ..In contrast, TSN reduced HSF1 phosphorylation and cell surface IGF-2R while elevating SIRT1 via ERs. TSN was capable of attenuating AngII-induced IGF-2R pathway and hypertrophy through ERs in H9c2 cardiomyoblast cells. ..
  32. Mousavi S, Fønhus M, Kindberg G, Tolleshaug H, Berg T. Enhanced activity of lysosomal proteases in activated rat hepatic stellate cells is associated with a concomitant increase in the number of the mannose-6-phosphate/insulin-like growth factor II receptor. Cell Biol Int. 2013;37:703-12 pubmed publisher
    ..Degradation of the ligand was reduced by inhibitors of lysosomal proteases and therefore took place in lysosomes. ..
  33. Morvan J, Köchl R, Watson R, Collinson L, Jefferies H, Tooze S. In vitro reconstitution of fusion between immature autophagosomes and endosomes. Autophagy. 2009;5:676-89 pubmed
    ..We also demonstrate that the lipidated form of the autophagosomal protein LC3 is dispensable for this fusion event. ..
  34. Villevalois Cam L, Rescan C, Gilot D, Ezan F, Loyer P, Desbuquois B, et al. The hepatocyte is a direct target for transforming-growth factor beta activation via the insulin-like growth factor II/mannose 6-phosphate receptor. J Hepatol. 2003;38:156-63 pubmed
  35. Mills J, Falls J, De Souza A, Jirtle R. Imprinted M6p/Igf2 receptor is mutated in rat liver tumors. Oncogene. 1998;16:2797-802 pubmed
    We have previously shown that inactivation of mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) is a common early event in both human liver and breast carcinogenesis...
  36. Orsi A, Razi M, Dooley H, Robinson D, Weston A, Collinson L, et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell. 2012;23:1860-73 pubmed publisher
  37. Corvera S, Folander K, Clairmont K, Czech M. A highly phosphorylated subpopulation of insulin-like growth factor II/mannose 6-phosphate receptors is concentrated in a clathrin-enriched plasma membrane fraction. Proc Natl Acad Sci U S A. 1988;85:7567-71 pubmed
    ..In addition, insulin action may prevent the concentration of these receptors in a clathrin-enriched membrane subfraction. ..
  38. Saito T, Akutsu S, Urushiyama T, Ishibashi K, Nakagawa Y, Shuler C, et al. Changes in the mRNA expressions of insulin-like growth factors, their receptors, and binding proteins during the postnatal development of rat masseter muscle. Zoolog Sci. 2003;20:441-7 pubmed
    ..rat masseter muscle during the shift of rat feeding behavior, we analyzed the expressions of IGF-I, IGF-II, IGFR1, IGFR2, and IGFBP1~6 mRNAs in rat masseter muscle between 0 and 70 days after birth using the competitive, reverse ..
  39. Hawkes C, Kar S. Insulin-like growth factor-II/mannose-6-phosphate receptor: widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype. J Comp Neurol. 2003;458:113-27 pubmed
  40. Hankins G, De Souza A, Bentley R, Patel M, Marks J, Iglehart J, et al. M6P/IGF2 receptor: a candidate breast tumor suppressor gene. Oncogene. 1996;12:2003-9 pubmed
    The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) functions in the activation of TGFbeta, a potent growth inhibitor for most cell types, the degradation of the mitogen, IGF2, and the intracellular trafficking of ..