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Receptor, IGF Type 2MannoseMannosephosphatesReceptors, LysosphingolipidPhosphatesPropylene GlycolsHexosephosphatesSphingosineReceptors, LysophospholipidCathepsin DLysosomesLysophospholipidsMannose-Binding Lectinstrans-Golgi NetworkEndosomesReceptors, Cell SurfaceGuanosine Diphosphate MannoseInsulin-Like Growth Factor IICalcium PhosphatesGlucose-6-PhosphateSugar PhosphatesGolgi ApparatusGlyceraldehyde-3-Phosphate DehydrogenasesCationsEndocytosisDolichol Monophosphate MannoseGlucuronidaseMolecular Sequence DataOligosaccharidesAdaptor Proteins, Vesicular Transportalpha-MannosidaseKineticsAdaptor Protein Complex alpha SubunitsMannosidasesPhosphotransferases (Alcohol Group Acceptor)Amino Acid SequenceVesicular Transport ProteinsLysosome-Associated Membrane Glycoproteinsbeta-N-AcetylhexosaminidasesCell CompartmentationInositol PhosphatesBiological TransportCricetinaeCell LineMannose-6-Phosphate IsomeraseLectins, C-TypeCarbohydratesGlycosylationCoated Pits, Cell-MembraneCarrier Proteinsrab GTP-Binding ProteinsCell Membranealpha-GlucosidasesCattleHydrogen-Ion ConcentrationProtein BindingGlyceraldehyde 3-PhosphateMannosyltransferasesReceptors, G-Protein-CoupledBinding SitesCells, CulturedGlycoproteinsReceptors, SomatomedinHydrolasesPolyisoprenyl Phosphate SugarsPentose Phosphate PathwayMolecular WeightPolysaccharidesProtein TransportGlucosephosphate DehydrogenaseCoated VesiclesClathrinCarbohydrate MetabolismDihydroxyacetone PhosphateChromatography, AffinityCHO CellsPolyisoprenyl Phosphate MonosaccharidesCarbohydrate SequenceGlucose-6-Phosphate IsomeraseLigandsPhosphate Transport ProteinsRecombinant ProteinsAdaptor Protein Complex 1Adaptor Protein Complex gamma SubunitsGlucosephosphatesSorting NexinsPyridoxal PhosphateTransferases (Other Substituted Phosphate Groups)MannansPhosphorylationHexosaminidasesIntracellular MembranesCathepsin LLectinsTaurodeoxycholic AcidL Cells (Cell Line)FibroblastsOxadiazolesLiverMucolipidoses
IGF2RLigandProteinsLysosomesGolgiInsulin growthBindsEndothelial cellsIntracellularLysosomal enzymePathwayIGF2ResidueInternalizationAntibodiesLysosomeDeficiencyDegradationSecretoryAffinityDifferentialInteractionRegulationTYPEGeneCancerGrowth FactorMouseCellularRoleCell deathSpecificActsActivityEffectsPromoteTreatment
IGF2R8
  • Orthologous to human IGF2R (insulin like growth factor 2 receptor). (nih.gov)
  • The cation-independent mannose 6-phosphate (M6P)/Insulin-like growth factor-2 receptor (CI-MPR/IGF2R) is an ∼300 kDa transmembrane protein responsible for trafficking M6P-tagged lysosomal hydrolases and internalizing IGF2. (ox.ac.uk)
  • It is of note that rather than mediating intracellular signaling transduction elicited by IGF2, the IGF type 2 receptor (IGF2R) acts as a IGF2 scavenger. (hindawi.com)
  • The discovery that the gene-mannose 6-phosphate/insulin-like growthfactor II receptor (M6P/IGF2r)-acts as a tumor-suppressor genein human liver tumors could help researchers develop an earlydiagnostic test for liver cancer as well as new treatments, theresearchers said. (cancernetwork.com)
  • The protein receptor produced by M6P/IGF2r is an attractive targetbecause it is present on the cell surface and in the plasma, Jirtlesaid, making it readily accessible for use in both liver tumortherapy and diagnosis. (cancernetwork.com)
  • When working properly, the M6P/IGF2r receptor protein has at leastthree distinct regulatory roles within a cell, said Jirtle. (cancernetwork.com)
  • The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) is a multifunctional tumour suppressor which binds a variety of factors that impinge on the proliferation, migration and invasiveness of cancer cells. (boku.ac.at)
  • We have now demonstrated that reconstitution of functional M6P/IGF2R expression in receptor-deficient murine cancer cells severely compromises their invasive potential. (boku.ac.at)
Ligand3
  • This led to the identification of another mannose 6-phosphate binding receptor, the CD-MPR, which binds its ligand in the presence of a divalent cation such as Mn2+. (wikipedia.org)
  • The endosomal concentration of a mannose 6-phosphate receptor is unchanged in the absence of ligand synthesis. (rupress.org)
  • As a step towards their identification, we have recently established the individual importance of the different ligand-binding sites of the receptor for its anti-invasive properties. (boku.ac.at)
Proteins4
  • These results suggest that one of the functions of late endosomes is constitutive recycling of cell surface receptors through the Golgi apparatus if they fail to recycle to the cell surface directly from early endosomes, and that the late endosome recycling pathway is followed frequently by many rapidly internalized proteins. (rupress.org)
  • A high-mannose oligosaccharide precursor is synthesized and transferred to proteins in the endoplasmic reticulum and then processed in the Golgi apparatus ( 4 ). (frontiersin.org)
  • The receptor also works insidethe cell as a shuttle craft, moving proteolytic enzymes to thelysosomes, a part of the cellular digestive system that breaksdown proteins into simpler compounds. (cancernetwork.com)
  • In mammals, transport of CREG to these compartments was shown to rely on the M6P receptor pathway as typical for soluble lysosomal proteins. (boku.ac.at)
Lysosomes6
  • The mannose 6-phosphate receptors (MPRs) are transmembrane glycoproteins that target enzymes to lysosomes in vertebrates. (wikipedia.org)
  • Paula studied protein delivery to lysosomes at the Cambridge Institute of Medical Research for her first postdoc, and for her second she investigated the role of ubiquitin in the signalling and down-regulation of growth factor receptors at the Physiological Laboratory, University of Liverpool. (swansea.ac.uk)
  • Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). (abcam.com)
  • It binds to mannose-6-phosphate receptors and then is transported into lysosomes, then undergoes proteolytic cleavage that results in increased enzymatic activity and ability to cleave glycogen. (medscape.com)
  • Cerliponase alfa (rhTTP1), a proenzyme, is taken up by target cells in the CNS and is translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor). (centerwatch.com)
  • These results establish that CREG is a lysosomal protein that undergoes proteolytic maturation in the course of its biosynthesis, carries the M6P recognition marker and depends on the interaction with M6P receptors for efficient delivery to lysosomes. (boku.ac.at)
Golgi6
  • Mannose 6-phosphate receptors bind newly synthesized lysosomal hydrolases in the trans-Golgi network (TGN) and deliver them to pre-lysosomal compartments. (wikipedia.org)
  • In the Trans-Golgi a GlcNAc phosphotransferase (EC 2.7.8.17) adds a GlcNAc-1-phosphate residue onto the 6-hydroxyl group of a specific mannose residue within the oligosaccharide. (wikipedia.org)
  • In the trans-Golgi a phosphodiesterase (EC 3.1.4.45) will remove the GlcNAc residue exposing the mannose 6-phosphate tag, allowing the lysosomal enzymes to bind to the CI-MPR and the CD-MPR. (wikipedia.org)
  • thus enabling the receptors to bind to the lysosomal enzymes in the trans-Golgi and release them in the acidified environment of the endosome. (wikipedia.org)
  • The cation-independent mannose 6-phosphate receptor and the low density lipoprotein receptor, both rapidly internalized from the cell surface, and the synaptic vesicle membrane protein synaptophysin, were transported to the Golgi apparatus with equivalent, nonlinear kinetics. (rupress.org)
  • Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. (abcam.com)
Insulin growth1
  • We have studied the recycling and the phosphorylation state of the insulin growth factor (IGF) II/mannose 6-phosphate (Man-6-P) receptor in microvascular endothelial cells from rat adipose tissue. (elsevierpure.com)
Binds1
  • Once it binds to a lysosomal enzyme the receptor becomes internalised rapidly. (wikipedia.org)
Endothelial cells2
Intracellular2
  • Both of these receptors bind terminal mannose 6-phosphate with similar affinity (CI-MPR = 7 μM, CD-MPR = 8 μM) and have similar signals in their cytoplasmic domains for intracellular trafficking. (wikipedia.org)
  • This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. (nih.gov)
Lysosomal enzyme2
  • Once the lysosomal enzyme has been translocated into the rough endoplasmic reticulum an oligosaccharide composed of Glc3Man9GlcNAc2 is transferred en bloc to the protein. (wikipedia.org)
  • This marker was later identified as a mannose-6-phosphate residue on the lysosomal enzyme that interacts with a specific receptor on the lysosomal membrane, which then triggers endocytosis into the lysosome. (medscape.com)
Pathway3
  • Its function here is to capture any mannose 6-phosphate tagged enzymes that have accidentally entered the secretory pathway. (wikipedia.org)
  • As an agonist of the retinoic-X receptor (RXR) pathway, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. (frontiersin.org)
  • We found that receptors in the Toll-like receptor pathway, such as Tlr2 and CD14, were increased under LPS and HSV stimulation. (frontiersin.org)
IGF23
  • A role for CIM6P/IGF2 receptor in memory consolidation and enhancement. (nih.gov)
  • Structure of the Human Cation-Independent Mannose 6-Phosphate/IGF2 Receptor Domains 7-11 Uncovers the Mannose 6-Phosphate Binding Site of Domain 9. (ox.ac.uk)
  • Remarkably the D7-11 structure matches an IGF2-bound state of the receptor, suggesting this may be an intrinsically stable conformation at neutral pH. (ox.ac.uk)
Residue1
Internalization2
  • The redistribution of IGF-II/Man-6-P receptors was not due to an inhibition of internalization which was in fact stimulated by PMA. (elsevierpure.com)
  • Mannose 6-phosphate receptor-mediated internalization and activation of prorenin by cardiac cells. (medecinesciences.org)
Antibodies2
  • The phosphorylation state of the IGF-II/Man-6-P receptor was determined by 32 P labeling of intact cells and immunoprecipitation with anti-receptor antibodies. (elsevierpure.com)
  • The cell-surface receptor FcγRIIIa is crucial to the efficacy of therapeutic antibodies as well as the immune response. (bvsalud.org)
Lysosome2
  • Therefore, Neufeld suggested that I-cell disease was caused by a deficiency in the enzymes that add a specific mannose 6-phosphate tag onto lysosomal enzymes so they can be targeted to the lysosome. (wikipedia.org)
  • Once the enzyme has dissociated from the mannose 6-phosphate receptor, it is translocated from the endosome to the lysosome where the phosphate tag is removed from the enzyme. (wikipedia.org)
Deficiency1
  • Los E, Ford GA. Galactose-1-Phosphate Uridyltransferase Deficiency. (medscape.com)
Degradation1
  • The MIT Domain of UBPY Constitutes a CHMP Binding and Endosomal Localization Signal Required for Efficient Epidermal Growth Factor Receptor Degradation. (swansea.ac.uk)
Secretory1
  • Also occurs in coagulation factor XII, 2 type IV collagenases, PDC-109, and cation-independent mannose-6-phosphate and secretory phospholipase A2 receptors. (embl.de)
Affinity3
  • Scatchard analysis showed these cells have over 2 x 10 6 receptors/cell with an affinity constant of 1 x 10 9 M -1 . (elsevierpure.com)
  • In the presence of phorbol myristate acetate (PMA), an activator of PKC and analog of diacylglycerol, IGF-II receptor number increased in the plasma membrane by 60% without changes in the binding affinity. (elsevierpure.com)
  • This increase in cell surface receptor number was confirmed by affinity cross-linking and 125 I-surface labeling studies, occurred with a half-time of 20 min, and was reversible upon withdrawal of PMA. (elsevierpure.com)
Differential1
  • ACE inhibition versus angiotensin type 1 receptor antagonism : differential effects on PAI-1 over time. (medecinesciences.org)
Interaction2
  • Granzyme B is crucial for rapid induction of cell death and apoptosis through interaction with mannose-6-phosphate receptor. (biolegend.com)
  • In this study, we focused on the interaction between ß-catenin and liver receptor homologue-1 (LRH-1) and designed and synthesized a series of LRH-1-derived peptides to develop inhibitors against Wnt/ß-catenin signaling. (bvsalud.org)
Regulation4
  • Phosphorylation of hormone receptors by protein kinase C (PKC) may be involved in the regulation of receptor recycling. (elsevierpure.com)
  • Furthermore, after down-regulation of cellular PKC levels by preincubation with PMA, PMA was unable to activate residual PKC activity in the membranous pool or increase IGF-II receptor number at the cell surface. (elsevierpure.com)
  • A molecular understanding of membrane traffic has broad implications for our understanding of growth control in cancer, receptor trafficking errors in heart disease, regulation of insulin secretion in diabetes and synaptic vesicle biogenesis and transport in neurological disorders. (stanford.edu)
  • The Ubiquitin Isopeptidase UBPY Regulates Endosomal Ubiquitin Dynamics and Is Essential for Receptor Down-regulation. (swansea.ac.uk)
TYPE1
  • Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. (medecinesciences.org)
Gene3
  • From NCBI Gene: This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. (nih.gov)
  • Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants. (cdc.gov)
  • Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study. (cdc.gov)
Cancer2
  • Targeting of the Interleukin-13 Receptor (IL-13R)α2 Expressing Prostate Cancer by a Novel Hybrid Lytic Peptide. (swansea.ac.uk)
  • Because the receptor is involved both in switching on a growthinhibitor and inactivating a growth factor, the researchers hypothesizedthat losing it might well predispose a cell to cancerous growth.Their past studies showing that the protein was abundantly presentin normal liver cells but nearly absent in cancer cells strengthenedtheir suspicion. (cancernetwork.com)
Growth Factor4
  • Enables insulin-like growth factor binding activity and mannose binding activity. (nih.gov)
  • Control of growth factor receptor dynamics by reversible ubiquitination. (swansea.ac.uk)
  • This is illustrated by the determination of the previously unknown structure of repeat 11 of the human mannose-6-phosphate/insulin-like growth factor II receptor (Man6P/IGFII-receptor), with 310 amino acids in the asymmetric unit, which was phased by soaking the crystals in a cryoprotectant solution containing halide anions. (rcsb.org)
  • Since in cirrhosis, platelet-derived growth factor receptor beta (PDGFRβ) is upregulated in the liver as well as the kidney, this study coupled Y27 to human serum albumin (HSA) substituted with PDGFRβ-recognizing peptides (pPB), and investigated its effect on PTH in cirrhotic rats. (ibecbarcelona.eu)
Mouse1
  • Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology. (nih.gov)
Cellular1
  • Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. (medecinesciences.org)
Role1
  • Interdomain clusters of histidine and proline residues may impart receptor rigidity and play a role in structural transitions at low pH. (ox.ac.uk)
Cell death1
  • Glycosylation of classical death receptors fine-tunes cell death programs. (nature.com)
Specific2
  • Studies of I-cell disease led to the discovery of the receptors that bind to this specific tag. (wikipedia.org)
  • Specific delivery of ROCK-inhibitor Y-27632 (Y27) to HSC targeting mannose-6-phosphate-receptors reduces portal pressure and fibrogenesis. (ibecbarcelona.eu)
Acts1
  • Also acts as a receptor for neurotensin. (abcam.com)
Activity1
  • The effect of PMA on IGF-II receptor recycling correlated with its stimulation of PKC activity. (elsevierpure.com)
Effects1
  • Bexarotene (Bxt) is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favorable safety profile whose effects have been recently investigated in other neurodegenerative diseases. (frontiersin.org)
Promote1
  • Thus, PKC-stimulated serine phosphorylation of IGF-II/Man-6-P receptor may promote the translocation of the receptor to the cell surface, whereas IGF-II-stimulated dephosphorylation of the receptor may lead to a decrease in the number of cell surface receptors. (elsevierpure.com)
Treatment1
  • In the basal state, the receptor was phosphorylated only on serine residues which was increased by 75% after treatment with PMA. (elsevierpure.com)