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Gene Review

IGF2R  -  insulin-like growth factor 2 receptor

Bos taurus

Synonyms: CI-MPR, CIMPR
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Disease relevance of IGF2R


High impact information on IGF2R

  • These mutations give rise to truncated receptor protein and significant amino acid substitutions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis [4].
  • The 300 kDa cation-independent mannose 6-phosphate receptor (CI-MPR) mediates the intracellular transport of newly synthesized lysosomal enzymes containing mannose 6-phosphate on their N-linked oligosaccharides [5].
  • Antibodies that recognize the cytoplasmic domain of either the CI-MPR or the CD-MPR routinely give membrane preparations that are approximately 50-fold enriched in each of the respective receptors, as determined by quantitative Western blotting [6].
  • Specificity of binding of clathrin adaptors to signals on the mannose-6-phosphate/insulin-like growth factor II receptor [7].
  • This signal is presumably responsible for the concentration of the M6P receptor, with bound lysosomal enzymes, into coated pits which bud from the trans-Golgi network, thus mediating efficient transfer of these enzymes to lysosomes [7].

Chemical compound and disease context of IGF2R

  • The mannose 6-phosphate/insulin-like growth factor II (M6P/IGF-II) receptor, which is expressed in particular upon HSC during fibrosis, may serve as a target-receptor for a potential carrier [8].
  • Binding of rgp140 and of corresponding rgp160 of HIV-1 to heparin- and DS-substituted (sulphated dextran beads; SDB) affinity matrices was inhibited by the soluble specific ligand and also by fetuin, asialofetuin or the anionic simple carbohydrate derivative mannose-6-phosphate (M6P) [9].

Biological context of IGF2R


Anatomical context of IGF2R

  • The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays a critical role in the trafficking of newly synthesized mannose 6-phosphate-containing acid hydrolases to the lysosome [14].
  • Two distinct types of adaptors, the HA-II adaptors (found in plasma membrane coated pits) and the HA-I adaptors (localized to Golgi coated pits) bind to the cytoplasmic portion of the 270 kd mannose 6-phosphate (M6P) receptor-a receptor which is concentrated in coated pits on both the plasma membrane and in the trans-Golgi network [7].
  • We have developed a method for the isolation of the subcellular organelles from bovine liver which are enriched in the cation-independent mannose 6-phosphate receptor (CI-MPR) and the cation-dependent mannose 6-phosphate receptor (CD-MPR) [6].
  • A series of chemically synthesized oligomannosides that contain mannose 6-phosphate residues were utilized as inhibitors of the binding of beta-galactosidase to high (CI-MPR, 215 kDa) and low (CD-MPR, 41-46 kDa) molecular mass mannose 6-phosphate receptor from bovine testes in order to probe the specificity of each receptor [15].
  • We also found that HSV produced small plaques on human fibroblasts derived from patients with pseudo-Hurler's polydystrophy, cells in which glycoproteins are not modified with M-6-P residues and yet production of infectious HSV particles was not altered in the pseudo-Hurler cells [1].

Associations of IGF2R with chemical compounds


Physical interactions of IGF2R

  • Although the receptors exhibited similar relative specificities for phosphomonoesters, phosphodiesters did not inhibit binding of ligand to CD-MPR and only weakly inhibited binding to CI-MPR [15].

Other interactions of IGF2R


Analytical, diagnostic and therapeutic context of IGF2R

  • Whereas gel filtration chromatography suggested that purified bovine IGF2R species exist in a monomeric form, native gel electrophoresis allowed for the separation of dimeric and monomeric forms of the receptors with distinct phosphomannosyl ligand binding characteristics [10].
  • Using biosensor analysis, IgY antibodies were shown to bind M6P/IGFII-R with high affinity (K(D) = 7.5 x 10(-9) M) [2].
  • A solid-phase competitive ELISA using bovine M6P/IGFII-R coated on 96-well microplates, allowed us to titrate the M6P/IGFII-R in human sera at a sensitivity of 300 ng/ml [2].
  • Labeling of Madin-Darby bovine kidney cells followed by immunoprecipitation of the CI-MPR and analysis of the corresponding tryptic phosphopeptides shows that the same serines are phosphorylated in vivo [13].
  • To further define the location of the Man-6-P binding sites and to determine the role of specific arginine residues in Man-6-P binding, site-directed mutagenesis was utilized to create truncated soluble forms of the M6P/IGF-II receptor in conjunction with either conservative (Lys) or nonconservative (Ala) replacement of arginine residues [17].


  1. Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission. Brunetti, C.R., Burke, R.L., Hoflack, B., Ludwig, T., Dingwell, K.S., Johnson, D.C. J. Virol. (1995) [Pubmed]
  2. High-affinity antibodies from hen's-egg yolks against human mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R): characterization and potential use in clinical cancer studies. Lemamy, G.J., Roger, P., Mani, J.C., Robert, M., Rochefort, H., Brouillet, J.P. Int. J. Cancer (1999) [Pubmed]
  3. Receptor-mediated hepatic uptake of M6P-BSA-conjugated triplex-forming oligonucleotides in rats. Ye, Z., Cheng, K., Guntaka, R.V., Mahato, R.I. Bioconjug. Chem. (2006) [Pubmed]
  4. M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. De Souza, A.T., Hankins, G.R., Washington, M.K., Orton, T.C., Jirtle, R.L. Nat. Genet. (1995) [Pubmed]
  5. Structure of uPAR, plasminogen, and sugar-binding sites of the 300 kDa mannose 6-phosphate receptor. Olson, L.J., Yammani, R.D., Dahms, N.M., Kim, J.J. EMBO J. (2004) [Pubmed]
  6. Isolation and characterization of membranes from bovine liver which are highly enriched in mannose 6-phosphate receptors. Messner, D.J., Griffiths, G., Kornfeld, S. J. Cell Biol. (1989) [Pubmed]
  7. Specificity of binding of clathrin adaptors to signals on the mannose-6-phosphate/insulin-like growth factor II receptor. Glickman, J.N., Conibear, E., Pearse, B.M. EMBO J. (1989) [Pubmed]
  8. Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Beljaars, L., Molema, G., Weert, B., Bonnema, H., Olinga, P., Groothuis, G.M., Meijer, D.K., Poelstra, K. Hepatology (1999) [Pubmed]
  9. Interactions of HIV-1 and HIV-2 envelope glycoproteins with sulphated polysaccharides and mannose-6-phosphate. Mbemba, E., Gluckman, J.C., Gattegno, L. Glycobiology (1994) [Pubmed]
  10. Dimerization of the insulin-like growth factor II/mannose 6-phosphate receptor. Byrd, J.C., Park, J.H., Schaffer, B.S., Garmroudi, F., MacDonald, R.G. J. Biol. Chem. (2000) [Pubmed]
  11. The insulin-like growth factor-II/mannose-6-phosphate receptor is present in fetal bovine tissues throughout gestation. Pfuender, M., Sauerwein, H., Funk, B., Kessler, U., Barenton, B., Schwarz, H.P., Hoeflich, A., Kiess, W. Domest. Anim. Endocrinol. (1995) [Pubmed]
  12. The bovine mannose 6-phosphate/insulin-like growth factor II receptor. Localization of mannose 6-phosphate binding sites to domains 1-3 and 7-11 of the extracytoplasmic region. Westlund, B., Dahms, N.M., Kornfeld, S. J. Biol. Chem. (1991) [Pubmed]
  13. Phosphorylation of the cytoplasmic domain of the bovine cation-independent mannose 6-phosphate receptor. Serines 2421 and 2492 are the targets of a casein kinase II associated to the Golgi-derived HAI adaptor complex. Méresse, S., Ludwig, T., Frank, R., Hoflack, B. J. Biol. Chem. (1990) [Pubmed]
  14. The N-terminal carbohydrate recognition site of the cation-independent mannose 6-phosphate receptor. Olson, L.J., Dahms, N.M., Kim, J.J. J. Biol. Chem. (2004) [Pubmed]
  15. The binding specificity of high and low molecular weight phosphomannosyl receptors from bovine testes. Inhibition studies with chemically synthesized 6-O-phosphorylated oligomannosides. Distler, J.J., Guo, J.F., Jourdian, G.W., Srivastava, O.P., Hindsgaul, O. J. Biol. Chem. (1991) [Pubmed]
  16. Expression of IGF2 and IGF receptor mRNA in bovine nuclear transferred embryos. Han, D.W., Song, S.J., Uhum, S.J., Do, J.T., Kim, N.H., Chung, K.S., Lee, H.T. Zygote (2003) [Pubmed]
  17. The bovine mannose 6-phosphate/insulin-like growth factor II receptor. The role of arginine residues in mannose 6-phosphate binding. Dahms, N.M., Rose, P.A., Molkentin, J.D., Zhang, Y., Brzycki, M.A. J. Biol. Chem. (1993) [Pubmed]
  18. Major proteins of bovine seminal fluid bind to insulin-like growth factor-II. Desnoyers, L., Manjunath, P. J. Biol. Chem. (1994) [Pubmed]
  19. Differential effects of the anti-inflammatory compounds heparin, mannose-6-phosphate, and castanospermine on degradation of the vascular basement membrane by leukocytes, endothelial cells, and platelets. Bartlett, M.R., Cowden, W.B., Parish, C.R. J. Leukoc. Biol. (1995) [Pubmed]
  20. Improved in vitro bovine embryo development and increased efficiency in producing viable calves using defined media. Lim, K.T., Jang, G., Ko, K.H., Lee, W.W., Park, H.J., Kim, J.J., Lee, S.H., Hwang, W.S., Lee, B.C., Kang, S.K. Theriogenology (2007) [Pubmed]
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