Mannose 6‐<scp>P</scp>Receptors

Jirtle, Randy L.

doi:10.1002/047120918x.emb0880

Cited by 5 publications

(9 citation statements)

References 103 publications

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“…However, Ma et al (2004) created a transgenic mouse model carrying the human TNMD locus and pups displayed hyperglycemia only on paternal transmission of the gene. M6P/IGF2R (mannose 6-phosphate/insulin-like growth factor 2 receptor) maps to human chromosome 6q24.1 ] q24.3 and functions in intracellular lysosomal enzyme traffi cking, transforming growth factor beta activation and IGF2 degradation (Jirtle, 1999;Dahms and Hancock, 2002). In mice, raised levels of Igf2 arise from Igf2r defi ciency which results in cardiac abnormalities, cleft palate, fetal overgrowth and perinatal lethality (Filson et al, 1993;Jirtle, 1999).…”

Section: Human Chromosomementioning

confidence: 99%

“…M6P/IGF2R (mannose 6-phosphate/insulin-like growth factor 2 receptor) maps to human chromosome 6q24.1 ] q24.3 and functions in intracellular lysosomal enzyme traffi cking, transforming growth factor beta activation and IGF2 degradation (Jirtle, 1999;Dahms and Hancock, 2002). In mice, raised levels of Igf2 arise from Igf2r defi ciency which results in cardiac abnormalities, cleft palate, fetal overgrowth and perinatal lethality (Filson et al, 1993;Jirtle, 1999). In contrast, decreased Igf2r due to epigenetic changes in gene regulation result in large offspring syndrome (Young et al, 2001) suggesting a critical role in murine growth.…”

Section: Human Chromosomementioning

confidence: 99%

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Imprinted genes and their role in human fetal growth

Abu-Amero

Monk

Apostolidou

et al. 2006

Cytogenet Genome Res

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Growth is defined as the progressive increase in size and is listed as one of the eight main characteristics of life. In human gestation the most rapid growth phase is from 16 to 32 weeks when first there is both cell number and size increase and then from 32 weeks onwards there is continued size increase (Pollack and Divon, 1992). The mechanism of growth in utero is of fundamental interest to clinicians and scientists because of its implications for neonatal health. Growth is multifactorial in origin with both genetics and environment contributing equally large parts. Despite this complexity analysis of the candidate genes involved is possible using simple tissue biopsies at the relevant stages of development. Of particular interest in understanding fetal growth is the analysis of a group of genes that show a parent-of-origin effect known as genomic imprinting. Imprinted genes are not only found in eutherian (placental) and metatherian (marsupial) mammals but surprisingly also in plants. Nevertheless, their evolution in mammals appears to be linked primarily to placentation. It is thought to result from a potential conflict between the parents in terms of the drive to successfully propagate their own separate genes and the mother’s added drive for her survival through the pregnancy to reproduce again. This means that the mother wants to restrict fetal growth and the father to enhance it.

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Section: Human Chromosomementioning

confidence: 99%

Section: Human Chromosomementioning

confidence: 99%

Imprinted genes and their role in human fetal growth

Abu-Amero

Monk

Apostolidou

et al. 2006

Cytogenet Genome Res

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“…1,2 Homozygous M6PR null mice are both phenotypically normal and fertile, demonstrating that M6PR is not essential for either egg fertilization or organogenesis. 3,4 However, these animals exhibited defects in the targeting of multiple lysosomal enzymes, and increased levels of phosphorylated lysosomal enzymes are present in the body fluids.…”

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confidence: 99%

“…They include numerous lysosomal enzymes, the latent complex of transforming growth factor-␤ (TGF-␤), and granzyme B. 1,2,6 In addition to binding M6P-modified glycoproteins, M6P/ IGF2R also interacts specifically with several molecules through M6P-independent mechanisms. The best characterized of these is the mitogen insulin-like growth factor 2 (IGF2).…”

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confidence: 99%

Tissue-Specific Inactivation of Murine M6P/IGF2R

Wylie

Pulford

McVie‐Wylie

et al. 2003

The American Journal of Pathology

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The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and T cell-mediated immunity. M6P/IGF2R is an imprinted gene in mice with expression only from the maternal allele. Complete knockout of this gene causes neonatal lethality, thus preventing analysis of its multifunctional role postnatally. To help elucidate the biological functions of M6P/IGF2R in adulthood, we generated both complete and tissue-specific M6P/IGF2R knockout mice using the Cre/loxP system. We confirm that complete M6P/IGF2R knockout results in fetal overgrowth and neonatal lethality. In contrast, tissue-specific inactivation of this gene in either the liver or skeletal and cardiac muscle gives rise to viable animals with no obvious phenotype. The successful creation of viable tissue-specific M6P/IGF2R knockout mouse models will now allow for detailed analysis of receptor function in a number of cellular processes including brain development, carcinogenesis, lysosomal trafficking, and T cell-mediated immunity. Both the 275-kd cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) and the 46-kd cation-dependent mannose 6-phosphate receptor (M6PR) function in the intracellular trafficking of lysosomal enzymes.

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“…The mannose 6-phosphate/insulinlike growth factor 2 receptor (M6P/IGF2R) is mapped at the chromosome location 6q25-27 [3] , which is predicted to contain a liver tumor suppressor gene [4] . This gene encodes a receptor which functions in intracellular lysosomal enzyme trafficking, transforming growth factor beta (TGF-b) activation, and IGF2 degradation [5] . Granzyme B internalization by the M6P/IGF2R is also required for cytotoxic T cells to induce apoptosis in cells targeted for death, resulting in this receptor being referred to as a "death receptor" [6] .…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with primary hepatocellular carcinoma

Jang¹,

Kang²,

Choi³

et al. 2008

WJG

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AIM:To investigate the relationship between loss of heterozygosity (LOH) for mannose 6-phosphate/insulinlike growth factor 2 receptor (M6P/IGF2R) and the outcomes for primary HCC patients treated with partial hepatectomy. METHODS:The LOH for M6P/IGF2R in primary HCC patients was assessed using six different gene-specific nucleotide polymorphisms. The patients studied were enrolled to undergo partial hepatectomy.RESULTS: M6P/IGF2R was found to be polymorphic in 73.3% (22/30) of the patients, and of these patients, 50.0% (11/22) had tumors showing LOH in M6P/IGF2R. Loss of heterozygosity in M6P/IGF2R was associated with significant reductions in the two year overall survival rate (24.9% vs 65.5%; P = 0.04) and the disease-free survival rate (17.8% vs 59.3%; P = 0.03).

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Mannose 6‐PReceptors

Cited by 5 publications

References 103 publications

Imprinted genes and their role in human fetal growth

Imprinted genes and their role in human fetal growth

Tissue-Specific Inactivation of Murine M6P/IGF2R

Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with primary hepatocellular carcinoma

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