The mannose 6-phosphate/insulin-like growth factor-II (Man-6-P/IGF-II) receptor is known to cycle between the Golgi, endosomes, and the plasma membrane. In the Golgi the receptor binds newly synthesized lysosomal enzymes and transports them directly to an endosomal (prelysosomal) compartment without traversing the plasma membrane. Deletion of the carboxyl-terminal Leu-Leu-His-Val residues of the 163 amino acid cytoplasmic tail of the bovine Man-6-P/IGF-II receptor partially impaired this function, resulting in the diversion of a portion of the receptor-ligand complexes to the cell surface, where they were endocytosed. The same phenotype was observed when 134 residues of the cytoplasmic tail were deleted from the carboxyl terminus. Disruption of the Tyr24-Lys-Tyr-Ser-Lys-Val29 plasma membrane internalization signal alone had little effect on Golgi sorting, but when combined with either deletion resulted in a complete loss of this function. The mutant receptors retained the ability to recycle to ...
Human serum and urine contain polypeptides which bind mannose 6-phosphate (M6P) and insulin-like growth factor II (IGF II) and crossreact with antibodies against the M6P/IGF II receptor. These polypeptides are considered to be fragments of the M6P/IGF II receptor. The major Mr approx. 205,000 fragment in serum and urine is about 10 kDa smaller in size than the membrane-associated receptor and is accompanied by minor forms with Mr values ranging from 104,000 to 180,000. The presence of receptor fragments in biological fluids indicates that shedding is one of the mechanisms contributing to the turnover of the M6P/IGF II receptor and that receptor fragments are part of the heterogenous group of serum proteins whic bind IGF II. ...
Schmidt B, Kiecke-Siemsen C, Waheed A et al. (1995). "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. 270 (25): 14975-82. PMID 7797478. doi:10.1074/jbc.270.25.14975. CS1 održavanje: Eksplicitna upotreba et al. (link) ...
The study of dietary intake of vegetables and fruit and lung cancer risk in Harbin, Heilongjiang province, northeast China(b) and Tin Corporation (YTC) miners in Yunnan(c), showed a positive effect of intake of celery daily in reduced risk of lung cancer. According to Dr. Belanger JT. research, Perillyl alcohol, a monoterpene isolated from the essential oils of celery seeds, exhibited the effect of inducing apoptosis in tumor cells without affecting normal cells and reverting tumor cells back to a differentiated state in very cancer cells, including lung cancer, through increased mannose-6-phosphate/insulin-like growth factor II receptors, tissue growth factor beta receptors, Bak and decreased ras protein prenylation, ubiquinone synthesis, and induced Phase I and Phase II detoxification systems(d ...
The present study demonstrates that IR-A is a physiological receptor for IGF-II. Previously it was believed that most, if not all, biological effects of IGF-II in cells were mediated by IGF-I-R. IGF-II-R, which also binds mannose-6-phosphate residues, is devoid of tyrosine kinase activity and is not believed to have either metabolic or mitogenic signaling potential. Most studies have indicated that the IR, which is homologous to the IGF-I-R, binds IGF-II with a relatively low affinity (1 to 5% that of insulin) (45). However, there is evidence that in certain instances the IR can bind IGF-II with high affinity. "Atypical" IRs, which bind IGF-II with unusually high affinity, have been found in IM-9 lymphoblasts, immature erythrocytes (18), and fetal tissues (including human placenta and brain, and chicken embryo fibroblasts) (19). Furthermore, other studies suggest that during mouse fetal development, the growth promoting effect of IGF-II is mediated in part by signaling through the IR (28). By ...
The present study demonstrates that IR-A is a physiological receptor for IGF-II. Previously it was believed that most, if not all, biological effects of IGF-II in cells were mediated by IGF-I-R. IGF-II-R, which also binds mannose-6-phosphate residues, is devoid of tyrosine kinase activity and is not believed to have either metabolic or mitogenic signaling potential. Most studies have indicated that the IR, which is homologous to the IGF-I-R, binds IGF-II with a relatively low affinity (1 to 5% that of insulin) (45). However, there is evidence that in certain instances the IR can bind IGF-II with high affinity. "Atypical" IRs, which bind IGF-II with unusually high affinity, have been found in IM-9 lymphoblasts, immature erythrocytes (18), and fetal tissues (including human placenta and brain, and chicken embryo fibroblasts) (19). Furthermore, other studies suggest that during mouse fetal development, the growth promoting effect of IGF-II is mediated in part by signaling through the IR (28). By ...
definition of CIM6PR, what does CIM6PR mean?, meaning of CIM6PR, Cation-Independent Mannose 6-Phosphate Receptor, CIM6PR stands for Cation-Independent Mannose 6-Phosphate Receptor
It is well established that dynamin is involved in clathrin-dependent endocytosis, but relatively little is known about possible intracellular functions of this GTPase. Using confocal imaging, we found that endogenous dynamin was associated with the plasma membrane, the trans-Golgi network, and a perinuclear cluster of cation-independent mannose 6-phosphate receptor (CI-MPR)-containing structures. By electron microscopy (EM), it was shown that these structures were late endosomes and that the endogenous dynamin was preferentially localized to tubulo-vesicular appendices on these late endosomes. Upon induction of the dominant-negative dynK44A mutant, confocal microscopy demonstrated a redistribution of the CI-MPR in mutant-expressing cells. Quantitative EM analysis of the ratio of CI-MPR to lysosome-associated membrane protein-1 in endosome profiles revealed a higher colocalization of the two markers in dynK44A-expressing cells than in control cells. Western blot analysis showed that ...
In the fields of biochemistry and cell biology, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein that in humans is encoded by the M6PR gene. The CD-MPR is one of two transmembrane proteins that bind mannose-6-phosphate (M6P) tags on acid hydrolase precursors in the Golgi apparatus that are destined for transport to the lysosome. Homologues of CD-MPR are found in all eukaryotes. The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail. The extracytoplasmic/lumenal M6P binding-domain consists of 157 amino acid residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer. The cell surface receptor for insulin-like growth factor 2 also functions as a cation-independent mannose 6-phosphate receptor. It consists of fifteen repeats homologous to the ...
The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing). Igf2r null-allele maternal transmission results in placenta and heart over-growth and perinatal lethality (|90%) due to raised extra-cellular IGF2 secondary to impaired ligand clearance. It remains unknown if the phenotype is due to either ligand alone, or to both ligands. Here, we evaluate Igf2r specific loss-of-function of the domain-11 IGF2 binding site by replacing isoleucine with alanine in the CD loop (exon 34, I1565A), a mutation also detected in cancers. Igf2rI1565A/+p maternal transmission (heterozygote), resulted in placental and embryonic over-growth with reduced neonatal lethality (|60%), and long-term survival.
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1C39: Structural basis for recognition of phosphorylated high mannose oligosaccharides by the cation-dependent mannose 6-phosphate receptor.
Definition of Mannose-6-phosphate receptors with photos and pictures, translations, sample usage, and additional links for more information.
Lin SX, Mallet WG, Huang AY, Maxfield FR. Endocytosed cation-independent mannose 6-phosphate receptor traffics via the endocytic recycling compartment en route to the trans-Golgi network and a subpopulation of late endosomes ...
Analyses with the yeast two-hybrid system showed that the cytosolic tail of the human CI-MPR interacted with full-length GGA3 as well as with the ∼150-amino acid VHS domain, but not the GAT or GAE domains of GGA3 (Fig. 1C). Further analyses revealed that the CI-MPR tail interacted with the VHS domains of all three GGAs and that the CD-MPR tail interacted with the VHS domains of GGA1 and, more weakly, GGA3 (Fig. 1D). These interactions were highly specific, because neither MPR tail bound to the VHS domains of STAM1, HRS, TOM1, and TOM1L1 (Fig. 1D). Likewise, we did not detect interactions between the GGA VHS domains and the cytosolic tails of TGN38, TRP2, tyrosinase, TRP1, LAMP-2, LIMP II, low density lipoprotein (LDL) receptor, β-amyloid precursor, and transferrin receptor (Fig. 1D), which contain either tyrosine-based sorting signals or dileucine-based sorting signals devoid of acidic clusters.. Deletion of the acidic-cluster-dileucine signals from the CI-MPR and CD-MPR tails abolished ...
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. Sorting of mannose 6-phosphate receptors mediated by the GGAs.
IN-ADP1.5/2.0 IN-BATT-3 IN-CF-E9677 IN-CF-F9677 IN-CF-G9677 IN-FBLOCK-96 IN-G10 IN-G20 IN-G50 IN-H2O3 -96L IN-H2O3-100C IN-H2O3-100CB IN-H2O3-96 IN-H2O3-96B IN-H2O3-H IN-H2O3-HB IN-H2O3-PRO IN-H2O3-PROB IN-H2O3-PROIII IN-H2O3-PROIIIB IN-HBLOCK-15 IN-HBLOCK-50 IN-M8RT IN-Pad3-100C IN-Pad3-3H IN-Pad3-H IN-Pad3-H-135C IN-PES-50 IN-PES-ST IN-QBLOCK-0.2 IN-QBLOCK-0.5 IN-QBLOCK-1.5 IN-QBLOCK-2.0 IN-THEATER4x4 Instrument MPR-504 Instrument MPR-506 Instrument MPS-800 Instrument MPW-30 Instrument MPW-60 Instrument MPW-WH-1 Instrument MPR-504 Instrument MPR-506 Instrument MPS-800 Instrument MPW-30 Instrument MPW-60 Instrument MPW-WH-1 IN-ADP1.5/2.0 IN-BATT-3 IN-CF-E9677 IN-CF-F9677 IN-CF-G9677 IN-FBLOCK-96 IN-G10 IN-G20 IN-G50 IN-H2O3 -96L IN-H2O3-100C IN-H2O3-100CB IN-H2O3-96 IN-H2O3-96B IN-H2O3-H IN-H2O3-HB IN-H2O3-PRO IN-H2O3-PROB IN-H2O3-PROIII IN-H2O3-PROIIIB IN-HBLOCK-15 IN-HBLOCK-50 IN-M8RT IN-Pad3-100C IN-Pad3-3H IN-Pad3-H IN-Pad3-H-135C IN
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Taken together, our results identify the IGF-Trap as a potent inhibitor of the growth of several highly aggressive carcinoma cell types. Moreover, in our hands, the tumor-inhibitory effect of the IGF-Trap was superior to that of an anti-IGFIR antibody administered at the same (or higher) concentrations, as evidenced by the complete growth arrest and/or regression of established human breast carcinomas in IGF-Trap-treated, but not in antibody-treated xenotransplanted mice. The anticancer effect of the IGF-Trap also compared favorably with IGFBP-1 that bound IGFI and IGFII with affinities comparable with the IGF-Trap but could not significantly inhibit the growth of colorectal carcinoma MC-38 liver metastases relative to untreated controls, even when administered at a 10-fold higher concentration and with higher frequency than the IGF-Trap. This greater therapeutic efficacy is probably due to several factors, namely (i) the high affinity of the IGF-Trap for IGFII that results in blockade of both ...
Recombinant protein of human mannose-6-phosphate receptor (cation dependent) (M6PR), 20 ug available for purchase from OriGene - Your Gene Company.
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TY - JOUR. T1 - Measurement of insulin-like growth factor-II in physiological fluids and tissues. II. extraction and quantification in rat tissues. AU - Lee, Wei Hua. AU - Bowsher, Ronald R.. AU - Apathy, John M.. AU - Smith, Michele C.. AU - Henry, David P.. PY - 1991/2. Y1 - 1991/2. N2 - The tissue distribution and developmental patterns of insulin-like growth factor-II (IGF-II) have not been investigated in rat tissues, primarily because of the lack of an efficient extraction method for IGF-II and a sensitive RIA. IGF- II was extracted from rat tissues by formic acid, and the extract was heated at an acidic pH and treated with acetone. The removal of binding proteins was demonstrated by fast protein liquid chromatography size exclusion column and the elimination of a dilutional bias in the RIA. Using rat IGF-II as standard, we optimized a RIA for the quantification of IGF-II in rat tissues. In adult rats, IGF-II was found in all 15 tissues examined, with the highest concentration in the ...
J:45195 Melnick M, Chen H, Buckley S, Warburton D, Jaskoll T, Insulin-like growth factor II receptor, transforming growth factor-beta, and Cdk4 expression and the developmental epigenetics of mouse palate morphogenesis and dysmorphogenesis. Dev Dyn. 1998 Jan;211(1):11-25 ...
Loss of Imprinting of Insulin-like Growth Factor-II in Wilms Tumor Commonly Involves Altered Methylation but not Mutations of CTCF or Its Binding ...
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Biosynthesis of myeloperoxidase (MPO), a myeloid lysosomal hemoprotein critical for the optimal oxygen-dependent microbicidal activity of human neutrophils, is incompletely understood. The primary translation product undergoes cotranslational N-linked glycosylation with subsequent insertion of the Fe-containing prosthetic group into the peptide backbone, thereby converting the enzymatically inactive, heme- free apoproMPO into the peroxidatively active precursor, proMPO. Eventually, proMPO undergoes proteolytic processing into native, lysosomal MPO, with subunits of 59 and 13.5 Kd. We studied three unanswered questions regarding MPO biosynthesis: (1) At what point during MPO biosynthesis is the heme moiety inserted into the apoenzyme? (2) What consequences does heme-insertion have on subsequent processing events? (3) What role does the mannose-6-phosphate receptor (M6PR) system play in the delivery of MPO to the lysosome? Disruption of Golgi by brefeldin A (BFA) produced two major changes in MPO ...
Definition of mannose-6-phosphate receptors. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
Arighi CN, Hartnell LM, Aguilar RC, Haft CR, Bonifacino JS. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor ...
Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon, and liver cancer. As IGF-II can deliver a mitogenic signal through both IGF-IR and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is a potential alternative option to IGF-IR-directed agents. Using a Fab-displaying phage library and a biotinylated precursor form of IGF-II (1-104 amino acids) as a target, we isolated Fabs specific for the E-domain COOH-terminal extension form of IGF-II and for mature IGF-II. One of these Fabs that bound to both forms of IGF-II was reformatted into a full-length IgG, expressed, purified, and subjected to further analysis. This antibody (DX-2647) displayed a very high affinity for IGF-II/IGF-IIE (K(D) value of 49 and 10 pmol/L, respectively) compared with IGF-I (approximately 10 nmol/L) and blocked binding of IGF-II to IGF-IR, IR-A, a panel of ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
S1pr5 - S1pr5 (untagged ORF) - Rat sphingosine-1-phosphate receptor 5 (S1pr5), (10 ug) available for purchase from OriGene - Your Gene Company.
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TY - JOUR. T1 - Insulin-like growth factor-II in nonislet cell tumors associated with hypoglycemia. T2 - Increased levels of messenger ribonucleic acid. AU - Lowe, William L.. AU - Roberts, Charles T.. AU - Leroith, Derek. AU - Rojeski, Maria T.. AU - Merimee, Thomas J.. AU - Fui, Serge Teng. AU - Keen, Harry. AU - Arnold, Dagmar. AU - Mersey, James. AU - Gluzman, Sheldon. AU - Spratt, Daniel. AU - Eastman, Richard C.. AU - Roth, Jesse. PY - 1989/12. Y1 - 1989/12. N2 - The role of insulin-like growth factor-II (IGFII) in the hypoglycemia associated with nonislet cell tumors is controversial. In this study we have addressed this question by measuring the IGF-II mRNA levels in extracts of these tumors. Hybridization of a 32P-labeled IGF-II cDNA to a Northern blot of RNA from three nonislet cell tumors associated with hypoglycemia (a hemangiopericytoma, fibrosarcoma, and malignant mesenchymal tumor) demonstrated six hybridizing bands, 6.8, 5.6, 4.7, 3.6, 2.6, and 2.1 kilobases in length. These ...
The objective of this proposal is to determine the prognostic role of expression of Insulin-Like Growth factor II in breast cancer. IGF-II is a potent mitogen for breast tumor epithelium, and is expressed in the stroma of invasive breast cancers. In this study, we analyzed expression of IGF-II mRNA and protein in two separate series of patients with invasive breast cancer, and compared the result with other clinical parameters, prognostic indicators and patient outcome. IGF-II mRNA and protein expression were easily detected in the majority of the 193 cases that were informative and had complete clinical follow up. While analysis of the cases from the two data sets individually showed that IGF-II expression was associated with clinical outcome depending on hormone receptor status. However, IGF-II expression by itself was not a prognostic indicator, and the relationship with hormone receptor status was lost when the separate data sets were analyzed together. We were unable to prove our initial hypothesis
Bevan, S. J., Parry-Billings, M, Opara, Elizabeth, Liu, C. T., Dunger, D. B. and Newsholme, E. A. (1992) The effect of insulin-like growth factor II on glucose uptake and metabolism in rat skeletal muscle in vitro. Biochemical Journal, 286(2), pp. 561-565. ISSN (print) 0264-6021 ...
The retromer is a phylogenetically conserved multisubunit complex that mediates retrograde transport of transmembrane cargo from endosomes to the TGN (Seaman, 2005; Bonifacino and Rojas, 2006; Bonifacino and Hurley, 2008). The best-characterized cargo for the mammalian retromer is the cation-independent mannose 6-phosphate receptor (MPR [CI-MPR]), one of two intracellular sorting receptors that participates in the delivery of acid hydrolases to lysosomes (Kornfeld, 1992). The CI-MPR binds newly synthesized acid hydrolases at the TGN and carries them within clathrin-coated vesicles to endosomes, where the hydrolases are released for eventual transport to lysosomes. The retromer functions to retrieve the unoccupied receptors to the TGN, where they engage in further cycles of acid hydrolase sorting. Depletion of retromer subunits by RNAi prevents this retrieval, leading to rerouting of the receptors to lysosomes and consequent leakage of newly synthesized acid hydrolases into the extracellular ...
Reagents and antibodies. Mouse Laminin-1, Lipofectin, LipofectAMINE, and LipofectAMINE 2000 were purchased from Invitrogen (Carlsbad, CA). Recombinant human IGF-I or IGF-II (rhIGF-II) was purchased from R&D System, Inc. (Minneapolis, MN) or Austral Biologics (San Ramon, CA), respectively. Human FN was purified as described ( 33). Bovine serum albumin (BSA) was purchased from Sigma (St. Louis, MO). Wortmannin was purchased from Calbiochem (La Jolla, CA).. The following monoclonal antibodies (mAbs) were used: to human β1 integrin P4C10 (Chemicon, Temecula, CA), clone-18 (BD Biosciences, San Jose, CA), and TS2/16 [American Type Culture Collection (ATCC), Manassas, VA]; to chicken β1 integrin W1B10 (Sigma Chemical Co., St. Louis, MO); to human β4 integrin A9 (kindly provided by Dr. L. Shaw); to hemagglutinin 12CA5 (ATCC); to a vascular endothelial surface protein 1C10 (Life Technologies, Inc., Gaithersburg, MD); to c-myc; to β-tubulin (Sigma). The following rabbit polyclonal antibodies were ...
Lysosomes are membrane-delimited organelles in animal cells serving as the cells main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than 40 hydrolases in an acidic environment (pH of about 5). After synthesis in the ER, lysosomal enzymes are decorated with mannose-6-phosphate residues, which are recognized by mannose-6-phosphate receptors in the trans-Golgi network. They are packaged into clathrin-coated vesicles and are transported to late endosomes. Substances for digestion are acquired by the lysosomes via a series of processes including endocytosis, phagocytosis, and autophagy ...
We conclude that through coincidence detection SNX1 associates with a microdomain of the early endosome-characterized by high membrane curvature and the presence of 3-phosphoinositides-from where it regulates tubular-based endosome-to-TGN retrieval of the CI-MPR.
Expression of IGF2R (CD222, CI-M6PR, CI-MPR, CIMPR, M6P-R, MPR1, MPR300, MPRI) in bronchus tissue. Antibody staining with HPA011332 and CAB009661 in immunohistochemistry.
Expression of IGF2R (CD222, CI-M6PR, CI-MPR, CIMPR, M6P-R, MPR1, MPR300, MPRI) in soft tissue tissue. Antibody staining with HPA011332 and CAB009661 in immunohistochemistry.
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This Igf1-Lr3 Protocol and workout routine has helped my personal training clients, and myself build monster calves. Train calves 3x/week and administer 100mcg Igf1-Lr3 post workout in a series of micro injections into each calve muscle spread out about 1/2 from each other. Each calve will get 10 injects each consisting of 5mcg Igf1-Lr3 per inject site. CALVE WORKOUT I find the best response from calves comes by training them 3 times a week, hitting only one exercise per
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Das IGF1R-Gen kodiert einen Rezeptor mit Tyrosinkinase-Aktivität, der insbesondere von dem Insulin-ähnlichen Wachstumsfaktor (IGF1) stimuliert werden kann. Mutationen führen zur autosomal dominanten oder rezessiven IGF1-Resistenz. Neben der Wachstumsregulation scheint der Rezeptor auch eine Bedeutung für die Steuerung der Apoptose zu besitzen. Meist kann man ihn besonders zahlreich in bosartigem Tumorgewebe finden.. ...
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摘要 旨在研究山羊体细胞核移植对克隆后代成纤维细胞IGF2-H19基因座甲基化的影响。以奶山羊耳成纤维细胞(GFC,对照组)和克隆山羊耳成纤维细胞(CFC,试验组)为试验材料,培养至第5代时,采用细胞计数法绘制细胞生长曲线,流式细胞仪检测细胞凋亡情况,实时荧光定量PCR分析基因的表达差异,亚硫酸氢盐测序(BSP)分析差异甲基化区域的甲基化水平。结果显示,GFC和CFC组细胞的生长曲线均呈典型S型,但CFC组细胞的凋亡率显著高于GFC组(P,0.01);CFC组细胞中Dnmt1(P,0.01)、Dnmt3b(P,0.01)、 ...
4AQ0: A Bacterial Glycosidase Enables Mannose-6-Phosphate Modification and Improved Cellular Uptake of Yeast-Produced Recombinant Human Lysosomal Enzymes.