Endocytosis of Insulin-like Growth Factor II by a Mini-receptor Based on Repeat 11 of the Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor

Grimme, Susanne; Höning, Stefan; Figura, Kurt Von; Schmidt, Bernhard

doi:10.1074/jbc.m003789200

Cited by 15 publications

(11 citation statements)

References 49 publications

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“…However, this effort was unsuccessful due to apparent instability of the full-length LRP1B cDNA. Because minireceptors of several large cell surface receptors, such as LRP and insulin-like growth factor receptor II, have been used successfully for functional analyses (25,27,28,31,32), especially of individual domains, we generated a minireceptor of LRP1B containing domain IV, the transmembrane domain, and the cytoplasmic tail (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

The Putative Tumor Suppressor LRP1B, a Novel Member of the Low Density Lipoprotein (LDL) Receptor Family, Exhibits Both Overlapping and Distinct Properties with the LDL Receptor-related Protein

Liu

Obermoeller-McCormick

et al. 2001

Journal of Biological Chemistry

130

150

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The low density lipoprotein receptor-related proteindeleted in tumor (LRP1B, initially referred to as LRP-DIT) was cloned and characterized as a candidate tumor suppressor. It is a new member of the low density lipoprotein receptor gene family. Its overall domain structure and large size (ϳ600 kDa) are similar to LRP and suggest that it is a multifunctional cell surface receptor. Herein, we characterize a series of ligands for the receptor using cell lines that stably express it as a domain IV minireceptor (mLRP1B4). Ligands of LRP including receptor-associated protein, urokinase plasminogen activator, tissue-type plasminogen activator, and plasminogen activator inhibitor type-1 each demonstrate binding, internalization, and degradation via mLRP1B4. Interestingly, the kinetics of ligand endocytosis is distinctly different from that of LRP, with LRP1B exhibiting a markedly diminished internalization rate. In addition, tissue expression analysis reveals that the LRP1B gene is expressed in brain, thyroid, and salivary gland. These studies thus extend the physiological roles of members of the LDL receptor family.Members of the low density lipoprotein receptor gene family play a wide variety of roles in normal cell function and development. For example, mutations of the low density lipoprotein receptor gene, the prototypic family member, result in the genetic disease familial hypercholesterolemia (1). Much attention has focused on other members of this gene family (including LRP, 1 megalin, apolipoprotein E receptor-2, very low density lipoprotein receptor) because of their recently recognized roles in development, cell signaling, and pathogenesis (2, 3). The low density lipoprotein receptor-related protein LRP1B (initially referred to as LRP-DIT (deleted in tumor)), a candidate tumor suppressor, is a new member of the giant receptor subgroup of this gene family. It is located at chromosome 2q21.2 and was isolated by positional cloning based on homozygous deletions detected in human cancer cell lines (4 -6). Mutation analysis revealed that the gene is frequently (45%) inactivated in human non-small cell lung cancer cell lines by intragenic homozygous deletions, point mutations, and aberrant transcripts missing internal portions. Loss of heterozygosity analysis also detected high allelic loss within the locus using two independent microsatellite polymorphism markers, suggesting that the gene is a candidate tumor suppressor (4). The low density lipoprotein receptor gene family previously contained two very large members, LRP (LRP1), a dimer of 515 and 85 kDa, and its closely related homolog, megalin (LRP2), a single species of ϳ600 kDa (2, 3). LRP1B is more closely related to LRP (with similarity of 59 and 52% identity at the cDNA and predicted amino acid levels, respectively) than to LRP2 (4). The cDNA of LRP1B is 16.5 kilobases, with an open reading frame of 13,797 base pairs, which encodes a protein of 4599 amino acids. Characterization of exon-intron boundaries determined that the genomic DNA of LRP1B contains 91 e...

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Section: Resultsmentioning

confidence: 99%

The Putative Tumor Suppressor LRP1B, a Novel Member of the Low Density Lipoprotein (LDL) Receptor Family, Exhibits Both Overlapping and Distinct Properties with the LDL Receptor-related Protein

Liu

Obermoeller-McCormick

et al. 2001

Journal of Biological Chemistry

130

150

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“…The functions of the IGFIIR in mammalian cells are to bind and internalize insulin-like growth factor II (IGFII) (26,36,43,75), to internalize and to sort lysosomal enzymes and other M6P-tagged proteins (11,12,24,45,46), and to regulate transforming growth factor ␤ activity (33,51). The majority of the receptor is found inside the cell, with only 5 to 10% located on the cell surface (45).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

et al. 2006

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The gram-positive bacterium Listeria monocytogenes causes a life-threatening disease known as listeriosis. The mechanism by which L. monocytogenes invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor CI M6PR or CD222) as a novel receptor for binding and invasion of Listeria species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized L. monocytogenes cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All Listeria spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by L. monocytogenes and L. innocua was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of Listeria spp. as affinity matrices. Adherence to and invasion of mammalian cells by L. monocytogenes was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of L. monocytogenes of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by L. monocytogenes may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.The gram-positive bacterium Listeria monocytogenes is a human pathogen that causes listeriosis primarily in immunosuppressed individuals. Symptoms are flu-like, and yet disease may progress to severe complications such as meningitis, septicemia, spontaneous abortion, or listeriosis of the newborn (28,39,83). The number of cases of listeriosis range from 40 to 44 per year in Australia (3, 79) and average 100 per year in the United States (13). Although the incidence of listeriosis is low compared to that of other foodborne diseases, the associated mortality rate is high (approximately 30%) (39, 74, 83). Knowledge of the molecular mechanisms underlying the binding and internalization of Listeria spp. to host cells is limited. New antibiotic, vaccine, and diagnostic targets are needed to prevent and treat infection by Listeria spp., and understanding the processes of adherence and entry into cells is fundamental to defining appropriate preventative and therapeutic strategies.Random peptide phage display has been successfully employed to identify new receptors and receptor ligands (44,52,53,82) and in epitope mapping and mimicking of protein antigens and antibodies (16,42,61) and drug discovery (40,52,78). In this study we employed random peptide phage display in an attempt to identify novel surface antigens that may be used as therapeutic targets ...

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“…IGF-2 also binds to the IGF-1R, but Igf-1r (-/-) Igf-2(p-) double knockouts had even more severe growth retardation than the Igf-1r knockout, suggesting that IGF-2 also acts through another receptor, which was subsequently identified as the insulin receptor Liu et al, 1993;Morrione et al, 1997). IGF-2 binds with high affinity to the IGFtype 2 receptor (also known as the cation-independent mannose 6-phosphate receptor) in mammals (IGF-2R/CI-MPR) (Tong et al, 1988;Grimme et al, 2000). The IGF-2R is a single-chain protein consisting of a large extracellular domain and a small cytoplasmic tail that lacks kinase activity (Ludwig et al, 1995) and there is no compelling evidence to suggest a role for the IGF-2R/ CI-MPR in transducing IGF-2 signals (Filson et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo

Eivers¹,

McCarthy²,

Glynn³

et al. 2004

Int. J. Dev. Biol.

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The insulin-like growth factor (IGF) signalling pathway has been highly conserved in animal evolution and, in mammals and Xenopus, plays a key role in embryonic growth and development, with the IGF-1 receptor (IGF-1R) being a crucial regulator of the signalling cascade. Here we report the first functional role for the IGF pathway in zebrafish. Expression of mRNA coding for a dominant negative IGF-1R resulted in embryos that were small in size compared to controls and had disrupted head and CNS development. At its most extreme, this phenotype was characterized by a complete loss of head and eye structures, an absence of notochord and the presence of abnormal somites. In contrast, up-regulation of IGF signalling following injection of IGF-1 mRNA, resulted in a greatly expanded development of anterior structures at the expense of trunk and tail. IGF-1R knockdown caused a significant decrease in the expression of Otx2, Rx3, FGF8, Pax6.2 and Ntl, while excess IGF signalling expanded Otx2 expression in presumptive forebrain tissue and widened the Ntl expression domain in the developing notochord. The observation that IGF-1R knockdown reduced expression of two key organizer genes (chordin and goosecoid ) suggests that IGF signalling plays a role in regulating zebrafish organizer activity. This is supported by the expression of IGF-1, IGF-2 and IGF-1R in shield-stage zebrafish embryos and the demonstration that IGF signalling influences expression of BMP2b, a gene that plays an important role in zebrafish pattern formation. Our data is consistent with a common pathway for integration of IGF, FGF8 and anti-BMPs in early vertebrate development.

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Endocytosis of Insulin-like Growth Factor II by a Mini-receptor Based on Repeat 11 of the Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor

Cited by 15 publications

References 49 publications

The Putative Tumor Suppressor LRP1B, a Novel Member of the Low Density Lipoprotein (LDL) Receptor Family, Exhibits Both Overlapping and Distinct Properties with the LDL Receptor-related Protein

The Putative Tumor Suppressor LRP1B, a Novel Member of the Low Density Lipoprotein (LDL) Receptor Family, Exhibits Both Overlapping and Distinct Properties with the LDL Receptor-related Protein

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo

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