Gene Symbol: CI-MPR
Description: insulin like growth factor 2 receptor
Alias: CD222, CI-M6PR, CIMPR, M6P-R, M6P/IGF2R, MPR 300, MPR1, MPR300, MPRI, cation-independent mannose-6-phosphate receptor, 300 kDa mannose 6-phosphate receptor, CI Man-6-P receptor, IGF-II receptor, M6P/IGF2 receptor, insulin-like growth factor II receptor
Species: human
Products:     CI-MPR

Top Publications

  1. Kalscheuer V, Mariman E, Schepens M, Rehder H, Ropers H. The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nat Genet. 1993;5:74-8 pubmed
    ..The human IGF2R gene, another classic example of imprinting in mice, was found to be expressed from both alleles. We provide the first direct evidence for differential imprinting in the human and murine genome. ..
  2. Schiller H, Szekeres A, Binder B, Stockinger H, Leksa V. Mannose 6-phosphate/insulin-like growth factor 2 receptor limits cell invasion by controlling alphaVbeta3 integrin expression and proteolytic processing of urokinase-type plasminogen activator receptor. Mol Biol Cell. 2009;20:745-56 pubmed publisher
    ..We conclude that M6P/IGF2R controls cell invasion by regulating alphaV integrin expression and by accelerating uPAR cleavage, leading to the loss of the urokinase/vitronectin/integrin-binding site on uPAR. ..
  3. Killian J, Oka Y, Jang H, Fu X, Waterland R, Sohda T, et al. Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations. Hum Mutat. 2001;18:25-31 pubmed
    ..Three identified amino-acid variants in the M6P/IGF2R ligand-binding domains may be under selection in humans. ..
  4. Orsel J, Sincock P, Krise J, Pfeffer S. Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein. Proc Natl Acad Sci U S A. 2000;97:9047-51 pubmed
    ..Although crystallography will be needed to define the precise interaction interface, these data provide an initial structural basis for TIP47-CI-MPR association. ..
  5. 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
  6. Schmidt B, Kiecke Siemsen C, Waheed A, Braulke T, Von Figura K. Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor. J Biol Chem. 1995;270:14975-82 pubmed
    ..Residues 1508-1566, which are shared by the 23-kDa IGF-II-binding fragment and repeat 11, are proposed to form the IGF-II binding site of the M6P/IGF-II receptor. ..
  7. Kaku K, Osada H, Seki K, Sekiya S. Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth. Acta Paediatr. 2007;96:363-7 pubmed
    ..There was also a significant difference in birth weight among the three neonatal c.901C > G genotypes of the IGF2R gene; CC, CG and GG. These findings indicate that both IGF2 and IGF2R gene variants are associated with fetal growth. ..
  8. Shiba T, Takatsu H, Nogi T, Matsugaki N, Kawasaki M, Igarashi N, et al. Structural basis for recognition of acidic-cluster dileucine sequence by GGA1. Nature. 2002;415:937-41 pubmed
    ..This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein. ..
  9. Schaffer B, Lin M, Byrd J, Park J, MacDonald R. Opposing roles for the insulin-like growth factor (IGF)-II and mannose 6-phosphate (Man-6-P) binding activities of the IGF-II/Man-6-P receptor in the growth of prostate cancer cells. Endocrinology. 2003;144:955-66 pubmed
    ..The magnitude of each activity in a given cell type seems to determine whether the net effect of the IGF2R on cell growth is inhibitory or stimulatory. ..

More Information


  1. Brown J, Esnouf R, Jones M, Linnell J, Harlos K, Hassan A, et al. Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur. EMBO J. 2002;21:1054-62 pubmed
    ..The structure factors and coordinates of IGF2R domain 11 have been deposited in the Protein Data Bank (accession codes 1GP0 and 1GP3). ..
  2. Petry C, Ong K, Wingate D, Brown J, Scott C, Jones E, et al. Genetic variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height. Growth Horm IGF Res. 2005;15:363-8 pubmed
    ..There were no detectable differences in weights at 7 years. Allelic variation in the gly1619arg SNP of the IGF2R gene is associated with disparity in childhood stature which could reflect altered binding of IGF-II to its receptor. ..
  3. Carroll K, Hanna J, Simon I, Krise J, Barbero P, Pfeffer S. Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science. 2001;292:1373-6 pubmed
    ..Thus, a cytosolic cargo selection device may be selectively recruited onto a specific organelle, and vesicle budding might be coupled to the presence of an active Rab GTPase. ..
  4. Chen Z, Ge Y, Landman N, Kang J. Decreased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells. BMC Cancer. 2002;2:18 pubmed
    ..This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth. ..
  5. O Gorman D, Weiss J, Hettiaratchi A, Firth S, Scott C. Insulin-like growth factor-II/mannose 6-phosphate receptor overexpression reduces growth of choriocarcinoma cells in vitro and in vivo. Endocrinology. 2002;143:4287-94 pubmed
    ..Overall, the findings in this study are consistent with the hypothesis that the IGF-II/M6PR suppresses tumor growth. ..
  6. Morgan D, Edman J, Standring D, Fried V, Smith M, Roth R, et al. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987;329:301-7 pubmed
    ..The structural and biochemical features of the IGF-II receptor appear identical to those of the cation-independent mannose-6-phosphate receptor. ..
  7. Williams C, Rezgui D, Prince S, Zaccheo O, Foulstone E, Forbes B, et al. Structural insights into the interaction of insulin-like growth factor 2 with IGF2R domain 11. Structure. 2007;15:1065-78 pubmed
    ..The models reveal that the molecular interaction is driven by critical hydrophobic residues on IGF2 and IGF2R, while a ring of flexible, charged residues on IGF2R may modulate binding. ..
  8. Brown J, Delaine C, Zaccheo O, Siebold C, Gilbert R, van Boxel G, et al. Structure and functional analysis of the IGF-II/IGF2R interaction. EMBO J. 2008;27:265-76 pubmed
    ..Mutagenesis analyses confirm this IGF-II 'binding-hotspot', revealing that IGF-binding proteins and IGF2R have converged on the same high-affinity site. ..
  9. Chu C, Tzang B, Chen L, Kuo C, Cheng Y, Chen L, et al. IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells. J Endocrinol. 2008;197:381-90 pubmed publisher
    ..The suppression of IGF2R signaling pathways may be a good strategy to prevent the progression of pathological hypertrophy. ..
  10. Probst O, Puxbaum V, Svoboda B, Leksa V, Stockinger H, Mikula M, et al. The mannose 6-phosphate/insulin-like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells. Int J Cancer. 2009;124:2559-67 pubmed publisher
    ..These results indicate that the M6P/IGF2R status influences the metastatic propensity of squamous cell carcinomas. ..
  11. Crump C, Xiang Y, Thomas L, Gu F, Austin C, Tooze S, et al. PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic. EMBO J. 2001;20:2191-201 pubmed
    ..These studies demonstrate the requirement for PACS-1 interactions with adaptor proteins in multiple processes, including secretory granule biogenesis and HIV-1 pathogenesis. ..
  12. Oshima A, Nolan C, Kyle J, Grubb J, Sly W. The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells. J Biol Chem. 1988;263:2553-62 pubmed
  13. Motyka B, Korbutt G, Pinkoski M, Heibein J, Caputo A, Hobman M, et al. Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Cell. 2000;103:491-500 pubmed
    ..These results suggest a novel target for immunotherapy and a potential mechanism used by tumors for immune evasion. ..
  14. 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
    ..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. ..
  15. De Souza A, Hankins G, Washington M, Fine R, Orton T, Jirtle R. Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. Oncogene. 1995;10:1725-9 pubmed
    ..These results support the hypothesis that the M6P/IGFIIr gene may function as a tumor suppressor gene in the liver. ..
  16. Diaz E, Pfeffer S. TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking. Cell. 1998;93:433-43 pubmed
    ..These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi. ..
  17. Seaman M. Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J Cell Biol. 2004;165:111-22 pubmed
    ..The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin. ..
  18. 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
    ..M6P/IGF2R restricts liver cell invasion by preventing the pericellular action of M6P-modified proteins. ..
  19. Misra S, Puertollano R, Kato Y, Bonifacino J, Hurley J. Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains. Nature. 2002;415:933-7 pubmed
    ..The rigid spatial alignment of the three binding subsites leads to high specificity. ..
  20. Bucci C, Thomsen P, Nicoziani P, McCarthy J, van Deurs B. Rab7: a key to lysosome biogenesis. Mol Biol Cell. 2000;11:467-80 pubmed
    ..These data demonstrate for the first time that Rab7, controlling aggregation and fusion of late endocytic structures/lysosomes, is essential for maintenance of the perinuclear lysosome compartment. ..
  21. Sharma S, Bartholdson S, Couch A, Yusa K, Wright G. Genome-scale identification of cellular pathways required for cell surface recognition. Genome Res. 2018;28:1372-1382 pubmed publisher
  22. Gil Krzewska A, Wood S, Murakami Y, Nguyen V, Chiang S, Cullinane A, et al. Chediak-Higashi syndrome: Lysosomal trafficking regulator domains regulate exocytosis of lytic granules but not cytokine secretion by natural killer cells. J Allergy Clin Immunol. 2016;137:1165-1177 pubmed publisher
    ..LYST functions in the regulated exocytosis but not in the constitutive secretion pathway. ..
  23. Deissler H, Lang G, Lang G. Fate of the Fc fusion protein aflibercept in retinal endothelial cells: competition of recycling and degradation. Graefes Arch Clin Exp Ophthalmol. 2019;257:83-94 pubmed publisher
    ..Transport inhibition of aflibercept during cultivation without FBS is likely a consequence of an attenuated exocytosis due to decreased expression of Rab11. ..
  24. Tanaka Y, Suzuki G, Matsuwaki T, Hosokawa M, Serrano G, Beach T, et al. Progranulin regulates lysosomal function and biogenesis through acidification of lysosomes. Hum Mol Genet. 2017;26:969-988 pubmed publisher
    ..Our study provides new insights into the physiological function of PGRN and the role of PGRN insufficiency in the pathogenesis of neurodegenerative diseases. ..
  25. Lim P, Wert S, Tunc Ozcan E, Marr R, Ferreira A, Redei E. Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression. Behav Brain Res. 2018;353:242-249 pubmed publisher
    ..The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model. ..
  26. Cauvin C, Rosendale M, Gupta Rossi N, Rocancourt M, Larraufie P, Salomon R, et al. Rab35 GTPase Triggers Switch-like Recruitment of the Lowe Syndrome Lipid Phosphatase OCRL on Newborn Endosomes. Curr Biol. 2016;26:120-8 pubmed publisher
    ..We propose that the precise spatial and temporal activation of Rab35 acts as a major switch for OCRL recruitment on newborn endosomes, post-scission PtdIns(4,5)P2 hydrolysis, and subsequent endosomal trafficking. ..
  27. Frago S, Nicholls R, Strickland M, Hughes J, Williams C, Garner L, et al. Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist. Proc Natl Acad Sci U S A. 2016;113:E2766-75 pubmed publisher
    ..An evolved and reengineered high-specificity M6P/IGF2R domain 11 binding site for IGF2 may improve therapeutic targeting of the frequent IGF2 gain of function observed in human cancer. ..
  28. Cheng I, Stram D, Burtt N, Gianniny L, Garcia R, Pooler L, et al. IGF2R missense single-nucleotide polymorphisms and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 2009;18:1922-4 pubmed publisher
    ..None of these missense SNPs were significantly associated with breast cancer risk. Our findings provide no evidence that missense SNPs in IGF2R influence breast cancer susceptibility ..
  29. Jang H, Kang K, Choi B, Chai G, Hong S, Ha W, et al. Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with primary hepatocellular carcinoma. World J Gastroenterol. 2008;14:1394-8 pubmed
    ..9% vs 65.5%; P=0.04) and the disease-free survival rate (17.8% vs 59.3%; P=0.03). These results show M6P/IGF2R LOH predicts poor clinical outcomes in surgically resected primary HCC patients. ..
  30. Mauricio R, Srichai M, Axel L, Hochman J, Reynolds H. Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease. Clin Cardiol. 2016;39:596-602 pubmed publisher
    ..Abnormal myocardial perfusion reserve index (MPRI) was defined as global average ?1.84...
  31. Guan Y, Cai B, Wu X, Peng S, Gan L, Huang D, et al. microRNA-352 regulates collateral vessel growth induced by elevated fluid shear stress in the rat hind limb. Sci Rep. 2017;7:6643 pubmed publisher
  32. Li N, Luo H, Liu X, Ma S, Lin H, Chen R, et al. Association study of polymorphisms in FOXO3, AKT1 and IGF-2R genes with human longevity in a Han Chinese population. Oncotarget. 2016;7:23-32 pubmed publisher
    ..001, 2.3×10-26) .Therefore, the search for longevity-associated genes provides the identification of new potential targets beneficial for the treatment of diabetes. ..
  33. Franco F, Alves A, Godoy F, Avelar J, Rodrigues D, Pedroso T, et al. Evaluating genotoxic risks in Brazilian public health agents occupationally exposed to pesticides: a multi-biomarker approach. Environ Sci Pollut Res Int. 2016;23:19723-34 pubmed publisher
  34. Kiess W, Blickenstaff G, Sklar M, Thomas C, Nissley S, Sahagian G. Biochemical evidence that the type II insulin-like growth factor receptor is identical to the cation-independent mannose 6-phosphate receptor. J Biol Chem. 1988;263:9339-44 pubmed
    ..Our data support the conclusion that the type II IGF receptor and the cation-independent Man-6-P receptor are the same protein and that the IGF-II and Man-6-P-binding sites are distinct. ..
  35. Tian D, Mitchell I, Kreeger P. Quantitative analysis of insulin-like growth factor 2 receptor and insulin-like growth factor binding proteins to identify control mechanisms for insulin-like growth factor 1 receptor phosphorylation. BMC Syst Biol. 2016;10:15 pubmed publisher
  36. Kolarova J, Tangen I, Bens S, Gillessen Kaesbach G, Gutwein J, Kautza M, et al. Array-based DNA methylation analysis in individuals with developmental delay/intellectual disability and normal molecular karyotype. Eur J Med Genet. 2015;58:419-25 pubmed publisher
  37. Priya A, Sugatha J, Parveen S, Lacas Gervais S, Raj P, Gilleron J, et al. Essential and selective role of SNX12 in transport of endocytic and retrograde cargo. J Cell Sci. 2017;130:2707-2721 pubmed publisher
    ..This study therefore provides evidence for the existence of early endosomal subpopulations that have differential roles in the sorting of the cargoes along endocytic degradative pathways. ..
  38. Jahn S, Kashofer K, Thüringer A, Abete L, Winter E, Eidenhammer S, et al. Mutation Profiling of Usual Ductal Hyperplasia of the Breast Reveals Activating Mutations Predominantly at Different Levels of the PI3K/AKT/mTOR Pathway. Am J Pathol. 2016;186:15-23 pubmed publisher
    ..On the basis of evidence of activating mutations, loss of heterozygosity, and a mass forming proliferation, we propose that UDH is most appropriately viewed as an early neoplastic intraductal proliferation. ..
  39. Yermachenko A, Dvornyk V. UGT2B4 previously implicated in the risk of breast cancer is associated with menarche timing in Ukrainian females. Gene. 2016;590:85-9 pubmed publisher
    ..The obtained results provide evidence that UGT2B4, which was previously associated with predisposition to breast cancer, may play a role in the onset of menarche. ..
  40. Yun C, Tsai J, Tsai C, Mok G, Sun J, Hung C, et al. Qualitative and semi-quantitative evaluation of myocardium perfusion with 3 T stress cardiac MRI. BMC Cardiovasc Disord. 2015;15:164 pubmed publisher
    ..ROC analysis was used to determine the MPRI threshold that maximized sensitivity...
  41. Rose P, Bogyo M, Moses A, Fruh K. Insulin-like growth factor II receptor-mediated intracellular retention of cathepsin B is essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. J Virol. 2007;81:8050-62 pubmed
    ..In contrast to the increased cathepsin secretion observed in most other tumors, viral inhibition of CTSB secretion via induction of an M6PR is crucial for the transformation of endothelial cells. ..
  42. Dass S, Holloway C, Cochlin L, Rider O, Mahmod M, Robson M, et al. No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure. Circ Heart Fail. 2015;8:1088-93 pubmed publisher
    ..Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively...
  43. Ma P, De Waal E, Weaver J, Bartolomei M, Schultz R. A DNMT3A2-HDAC2 Complex Is Essential for Genomic Imprinting and Genome Integrity in Mouse Oocytes. Cell Rep. 2015;13:1552-60 pubmed publisher
    ..These results suggest seminal roles of HDAC1/2 in establishing maternal genomic imprints and maintaining genomic integrity in oocytes mediated in part through a SIN3A complex that interacts with DNMT3A2. ..
  44. Xu Y, Goodyer C, Deal C, Polychronakos C. Functional polymorphism in the parental imprinting of the human IGF2R gene. Biochem Biophys Res Commun. 1993;197:747-54 pubmed
    ..This is the first direct demonstration of imprinting as a polymorphic trait, a property that had been observed in transgene methylation and predicted from the behavior of certain human tumors. ..
  45. Gibson C, de Ruijter Villani M, Stout T. Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes. Placenta. 2017;57:175-182 pubmed publisher
    ..We propose that this ability to 'reset' conceptus development to uterine stage is an adaptation that explains why horse embryos are unusually tolerant of asynchrony after ET. ..
  46. Forbe B, McNeil K, Scott C, Surinya K, Cosgrove L, Wallace J. Contribution of residues A54 and L55 of the human insulin-like growth factor-II (IGF-II) A domain to Type 2 IGF receptor binding specificity. Growth Factors. 2001;19:163-73 pubmed
    ..Binding to the type I IGF receptor (IGF1R) and IGF binding protein-2 (IGFBP-2) is not altered. We can, therefore, conclude that residues at positions 54 and 55 in IGF-II are important for and equally contribute to IGF2R binding. ..
  47. Laureys G, Barton D, Ullrich A, Francke U. Chromosomal mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man and mouse. Genomics. 1988;3:224-9 pubmed
    ..The CIM6PR/IGF2R locus in man is asyntenic with the genes encoding IGF-II (IGF2), the IGF-I receptor (IGF1R), and the cation-dependent mannose 6-phosphate receptor (CDM6PR). ..
  48. Kim M, Deng H, Wong Y, Siddique T, Krainc D. The Parkinson's disease-linked protein TMEM230 is required for Rab8a-mediated secretory vesicle trafficking and retromer trafficking. Hum Mol Genet. 2017;26:729-741 pubmed publisher
  49. Chen A, Davis B, Sitrin M, Brasitus T, Bissonnette M. Transforming growth factor-beta 1 signaling contributes to Caco-2 cell growth inhibition induced by 1,25(OH)(2)D(3). Am J Physiol Gastrointest Liver Physiol. 2002;283:G864-74 pubmed
    ..Also, 1,25(OH)(2)D(3) sensitized Caco-2 cells to growth inhibitory effects of TGF-beta 1, contributing to the inhibition of Caco-2 cell growth by this secosteroid. ..
  50. Xhabija B, Vacratsis P. Receptor-mediated Endocytosis 8 Utilizes an N-terminal Phosphoinositide-binding Motif to Regulate Endosomal Clathrin Dynamics. J Biol Chem. 2015;290:21676-89 pubmed publisher
    ..These results further highlight the critical role for PI(3)P in the RME-8-mediated organizational control of various endosomal activities, including retrograde transport. ..
  51. 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. ..
  52. Bairey Merz C, Handberg E, Shufelt C, Mehta P, Minissian M, Wei J, et al. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J. 2016;37:1504-13 pubmed publisher
    ..coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo...
  53. Waguri S, Tomiyama Y, Ikeda H, Hida T, Sakai N, Taniike M, et al. The luminal domain participates in the endosomal trafficking of the cation-independent mannose 6-phosphate receptor. Exp Cell Res. 2006;312:4090-107 pubmed
    Although the role of the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CIMPR) has been well established in the receptor trafficking, that of the luminal domain is still controversial...
  54. Saeed H, Qiu W, Li C, Flyvbjerg A, Abdallah B, Kassem M. Telomerase activity promotes osteoblast differentiation by modulating IGF-signaling pathway. Biogerontology. 2015;16:733-45 pubmed publisher
    ..In conclusion, our data demonstrate that impaired IGF/AKT signaling contributes to the observed decreased bone mass and bone formation exhibited by telomerase deficient osteoblastic cells. ..
  55. Zhu Y, Doray B, Poussu A, Lehto V, Kornfeld S. Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor. Science. 2001;292:1716-8 pubmed
    ..The hinge domain of GGA2 bound clathrin, suggesting that GGA2 could be a link between cargo molecules and clathrin-coated vesicle assembly. Thus, GGA2 binding to the CI-MPR is important for lysosomal enzyme targeting. ..
  56. Chanprasertyothin S, Jongjaroenprasert W, Ongphiphadhanakul B. The association of soluble IGF2R and IGF2R gene polymorphism with type 2 diabetes. J Diabetes Res. 2015;2015:216383 pubmed publisher
    ..It was found that age, sex, and BMI were associated with beta cell function. In conclusion, IGF2R gene polymorphism and circulating IGF2R are associated with T2DM. ..
  57. Suh H, Lo Y, Choi N, Letendre S, Lee S. Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals. J Neuroinflammation. 2015;12:72 pubmed publisher
  58. Tikkanen R, Peltola M, Oinonen C, Rouvinen J, Peltonen L. Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase. EMBO J. 1997;16:6684-93 pubmed
    ..On the basis of the results of this and previous studies we suggest a general model for recognition of lysosomal enzymes by the phosphotransferase. ..
  59. van Rahden V, Brand K, Najm J, Heeren J, Pfeffer S, Braulke T, et al. The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module. Hum Mol Genet. 2012;21:5019-38 pubmed publisher
    ..Our data suggest that PI(4,5)P(2) dephosphorylation through OCRL regulates a Rac1-cofilin signalling cascade implicated in MPR trafficking from endosomes to the TGN. ..
  60. 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
  61. Takahashi Y, Mimori K, Yamamoto K, Watanabe M, Tanaka J, Kudo S, et al. Genomic copy number of a carcinogenic single nucleotide polymorphism at 8q24 in non-risk allele colorectal cancer associated with insulin growth factor 2 receptor expression. J Gastroenterol Hepatol. 2012;27 Suppl 3:95-9 pubmed publisher
    ..SNP at 8q24 makes diabetes a risk factor of CRC via IGF2R, especially in genetically non-risk allele cases. We speculate that the risk allele of 8q24 might be risky enough that diabetes is not necessary to worsen the risk for CRC. ..
  62. Wei Y, Li J, Huang J, Zhang X, Zhao H, Cui C, et al. Elevation of IGF-2 receptor and the possible underlying implications in end-stage heart failure patients before and after heart transplantation. J Cell Mol Med. 2012;16:1038-46 pubmed publisher
    ..Our preliminary studies suggest that elevation of IGF-2R may participate in pathological process of end-stage HF and involved in the acute cellular rejection after heart transplantation. ..
  63. Han Y, Luan B, Sun M, Guo L, Guo P, Tao J, et al. Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic modulation of vascular smooth muscle cells. J Mol Cell Cardiol. 2011;50:723-30 pubmed publisher
  64. Kokkonen N, Rivinoja A, Kauppila A, Suokas M, Kellokumpu I, Kellokumpu S. Defective acidification of intracellular organelles results in aberrant secretion of cathepsin D in cancer cells. J Biol Chem. 2004;279:39982-8 pubmed
    ..e. the cation-independent mannose-6-phosphate receptor (MPR300), was aberrantly distributed in acidification-defective MCF-7 cells...
  65. Dong X, Javle M, Hess K, Shroff R, Abbruzzese J, Li D. Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer. Gastroenterology. 2010;139:464-73, 473.e1-3 pubmed publisher
    ..This information may identify population subgroups that could benefit from IGF(1)R-targeted agents. ..
  66. Ishiwata T, Bergmann U, Kornmann M, Lopez M, Beger H, Korc M. Altered expression of insulin-like growth factor II receptor in human pancreatic cancer. Pancreas. 1997;15:367-73 pubmed
  67. Rojas R, Kametaka S, Haft C, Bonifacino J. Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors. Mol Cell Biol. 2007;27:1112-24 pubmed
  68. Tian Z, Yao G, Song H, Zhou Y, Geng J. IGF2R expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC. Cell Physiol Biochem. 2014;34:1578-88 pubmed publisher
    ..IGF2R silencing significantly enhanced the chemo-resistance of NSCLC cell lines to cisplatin treatment. The IGF2R expression in tumor is associated with the chemotherapy response and prognosis of Patients with advanced NSCLC. ..
  69. O Dell S, Day I. Insulin-like growth factor II (IGF-II). Int J Biochem Cell Biol. 1998;30:767-71 pubmed
    ..In the general adult population, the IGF2-INS gene cluster may also influence body weight, in which case IGF-II function could become a target for therapeutic intervention in obesity. ..
  70. Chang S, Tsai M, Huang F, Kung F. Expression of insulin-like growth factor (IGF), IGF receptor, and IGF-binding protein messenger ribonucleic acids in luteinized granulosa cells from different size follicles after controlled ovarian hyperstimulation. J Assist Reprod Genet. 2002;19:121-6 pubmed
    ..037). The increased levels of IGFBP-5 transcripts in luteinized granulosa cells found with increased follicular fluid volume after COH may favor a shift toward diminished action of IGFs in larger follicles immediately prior to ovulation. ..
  71. Di Bacco A, Gill G. The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor. Oncogene. 2003;22:5436-45 pubmed
  72. Hawkes C, Kar S. The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system. Brain Res Brain Res Rev. 2004;44:117-40 pubmed
  73. Vu T, Li T, Hoffman A. Promoter-restricted histone code, not the differentially methylated DNA regions or antisense transcripts, marks the imprinting status of IGF2R in human and mouse. Hum Mol Genet. 2004;13:2233-45 pubmed
    ..We discuss these findings in light of recent progress in identifying specific components of the epigenetic marks in imprinted genes. ..
  74. Kumar M, Kaur S, Nazir A, Tripathi R. HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling. Biochem Biophys Res Commun. 2016;474:137-145 pubmed publisher
    ..that Nef-GCC185 interaction disrupts Rab9 interaction resulting in delocalization of CI-MPR (cation independent Mannose 6 phosphate receptor) resulting in elevated secretion of hexosaminidase...
  75. Laube F. Mannose-6-phosphate/insulin-like growth factor-II receptor in human melanoma cells: effect of ligands and antibodies on the receptor expression. Anticancer Res. 2009;29:1383-8 pubmed
    ..Up-regulation of the tumour suppressor M6P/IGF-II receptor might represent an approach for anticancer therapy. In addition, results support recent data on the receptor's capability of signal transduction. ..
  76. Jeyaratnaganthan N, Højlund K, Kroustrup J, Larsen J, Bjerre M, Levin K, et al. Circulating levels of insulin-like growth factor-II/mannose-6-phosphate receptor in obesity and type 2 diabetes. Growth Horm IGF Res. 2010;20:185-91 pubmed publisher
    ..No acute effect of insulin was seen. These findings indicate that the IGF-II/M6P-R is nutritionally regulated, independently of IGF-II. ..
  77. Harris L, Crocker I, Baker P, Aplin J, Westwood M. IGF2 actions on trophoblast in human placenta are regulated by the insulin-like growth factor 2 receptor, which can function as both a signaling and clearance receptor. Biol Reprod. 2011;84:440-6 pubmed publisher
  78. Chen Y, Shao H, Li H, Han L, Zhang X. [Relationship of insulin-like growth factor receptor single nucleotide polymorphism (SNP) with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer]. Zhongguo Fei Ai Za Zhi. 2012;15:65-71 pubmed publisher
  79. 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
  80. Zhou Q, Mao Y, Jiang W, Chen Y, Huang R, Zhou X, et al. Development of IGF signaling antibody arrays for the identification of hepatocellular carcinoma biomarkers. PLoS ONE. 2012;7:e46851 pubmed publisher
    ..Our IGF signaling antibody array which can detect the expression of ten IGF family members with high sensitivity and specificity will undoubtedly prove a powerful tool for drug and biomarker discovery. ..
  81. Buckberry S, Bianco Miotto T, Hiendleder S, Roberts C. Quantitative allele-specific expression and DNA methylation analysis of H19, IGF2 and IGF2R in the human placenta across gestation reveals H19 imprinting plasticity. PLoS ONE. 2012;7:e51210 pubmed publisher
  82. Pfisterer K, Forster F, Paster W, Supper V, Ohradanova Repic A, Eckerstorfer P, et al. The late endosomal transporter CD222 directs the spatial distribution and activity of Lck. J Immunol. 2014;193:2718-32 pubmed publisher
    ..b>CD222, also known as the cation-independent mannose 6-phosphate/insulin-like growth factor 2 receptor, is the central ..
  83. Yang E, Qin L, Zhao Y, Zhang K, Chow P. Genetic changes and expression of the mannose 6-phosphate/insulin-like growth factor II receptor gene in human hepatitis B virus-associated hepatocellular carcinoma. Int J Mol Med. 2003;11:773-8 pubmed
    ..In the development of HBV-associated HCC, M6P/IGF2R mutation may not be a major agent. ..
  84. Zhang Y, Zhang Y, Xiao L, Yu T, Li J, Rao J, et al. Cooperative Repression of Insulin-Like Growth Factor Type 2 Receptor Translation by MicroRNA 195 and RNA-Binding Protein CUGBP1. Mol Cell Biol. 2017;37: pubmed publisher
    ..These findings indicate that IGF2R expression is controlled posttranscriptionally by two factors that associate with Igf2r mRNA and suggest that miR-195 and CUGBP1 dampen IGF signaling by inhibiting IGF2R translation. ..
  85. Wan L, Molloy S, Thomas L, Liu G, Xiang Y, Rybak S, et al. PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell. 1998;94:205-16 pubmed
    ..Cell-free assays indicate TGN localization of furin is directed by a PACS-1-mediated retrieval step. Together, these findings explain a mechanism by which membrane proteins in mammalian cells are localized to the TGN. ..
  86. Zhou G, Roizman B. Cation-independent mannose 6-phosphate receptor blocks apoptosis induced by herpes simplex virus 1 mutants lacking glycoprotein D and is likely the target of antiapoptotic activity of the glycoprotein. J Virol. 2002;76:6197-204 pubmed
    ..Instead, the data suggest that gD blocks the influx of lysosomal enzymes into the endosomal compartment by binding to CI-MPR. This conclusion is consistent with published reports that phosphorylated gD interacts with CI-MPR. ..
  87. Bartolac L, Lowe J, Koustas G, Grupen C, Sjoblom C. Vitrification, not cryoprotectant exposure, alters the expression of developmentally important genes in in vitro produced porcine blastocysts. Cryobiology. 2018;80:70-76 pubmed publisher
    ..Vitrification protocols that incorporated propanediol or a closed device were found to be least disruptive of gene expression in IVP porcine blastocysts. ..
  88. Takatsu H, Katoh Y, Shiba Y, Nakayama K. Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains. J Biol Chem. 2001;276:28541-5 pubmed
    ..These results indicate that GGA proteins regulate the localization to or exit from the TGN of the sorting receptors. ..