Chapter 24 Insulin‐Like Growth Factor‐2/Mannose‐6 Phosphate Receptors

El‐Shewy, Hesham M.; Luttrell, Louis M.

doi:10.1016/s0083-6729(08)00624-9

Cited by 79 publications

(72 citation statements)

References 186 publications

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“…Although the IGF-2R does not contain tyrosine kinase activity or an autophosphorylation site, there is evidence for the ability of cardiac IGF-2R to couple to G ␣q and induce cardiac hypertrophy (19,23). In the heart of the LBW, the elevated expression of the IGF-2R was associated with increased histone acetylation in critical regions of the IGF-2R gene.…”

Section: Discussionmentioning

confidence: 99%

IGF-2R-G_αqsignaling and cardiac hypertrophy in the low-birth-weight lamb

Wang

Tosh

Zhang

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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The cardiac insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy in a heterotrimeric G protein receptor-coupled manner involving ␣q (G␣q) or ␣s (G␣s). We have previously shown increased left ventricular weight and cardiac IGF-2 and IGF-2R gene expression in lowbirth-weight (LBW) compared with average-birth-weight (ABW) lambs. Here, we have investigated the cardiac expression of IGF-2 gene variants, the degree of histone acetylation, and the abundance of proteins in the IGF-2R downstream signaling pathway in ABW and LBW lambs. Samples from the left ventricle of ABW and LBW lambs were collected at 21 days of age. There was increased phosphoCaMKII protein with decreased HDAC 4 abundance in the LBW compared with ABW lambs. There was increased GATA 4 and decreased phospho-troponin I abundance in LBW compared with ABW lambs, which are markers of pathological cardiac hypertrophy and impaired or reduced contractility, respectively. There was increased histone acetylation of H3K9 at IGF-2R promoter and IGF-2R intron 2 differentially methylated region in the LBW lamb. In conclusion, histone acetylation of IGF-2R may lead to increased IGF-2R mRNA expression and subsequently mediate G ␣q signaling early in life via CaMKII, resulting in an increased risk of left ventricular hypertrophy and cardiovascular disease in adult life. low birth weight; insulin-like growth factor 2 receptor; histone acetylation

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Section: Discussionmentioning

confidence: 99%

IGF-2R-G_αqsignaling and cardiac hypertrophy in the low-birth-weight lamb

Wang

Tosh

Zhang

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…It is composed of a large extracytoplasmic domain and a short cytoplasmic tail that lacks intrinsic cytoplasmic activity (El-Shewy & Luttrell, 2009). IGF-IIR perform diverse cellular functions related to lysosome biogenesis and the regulation of growth and development.…”

Section: Introductionmentioning

confidence: 99%

New Biomarkers for Cervical Cancer – Perspectives from the IGF System

Serrano¹,

Umaña‐Pérez²,

Garay‐Baquero³

et al. 2012

Topics on Cervical Cancer With an Advocacy for Prevention

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“…The insulin-like growth factor II/cation-independent mannose 6-phosphate (IGF-II/CIM6P or IGF-II) receptor is a 250-kDa multifunctional glycoprotein that recognizes, via distinct sites, two different classes of ligands: (i) M6P-containing molecules, such as lysosomal enzymes, and (ii) IGF-II, a mitogenic polypeptide with structural homology to IGF-I and insulin (7)(8)(9). A subpopulation of the receptor located on the plasma membrane regulates internalization of IGF-II and various M6P-containing ligands for their subsequent clearance or activation.…”

mentioning

confidence: 99%

“…A subpopulation of the receptor located on the plasma membrane regulates internalization of IGF-II and various M6P-containing ligands for their subsequent clearance or activation. There is also evidence that the surface IGF-II receptor can mediate intracellular signaling in response to IGF-II binding (9)(10)(11). The majority of the receptors, however, localize within the EL system and function in the recognition of newly synthesized lysosomal enzymes in the trans-Golgi network (TGN) for sorting and delivery to endosomes/lysosomes.…”

mentioning

confidence: 99%

Overexpression of the Insulin-Like Growth Factor II Receptor Increases β-Amyloid Production and Affects Cell Viability

Wang

Buggia-Prévot

Zavorka

et al. 2015

Molecular and Cellular Biology

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dAmyloid ␤ (A␤) peptides originating from amyloid precursor protein (APP) in the endosomal-lysosomal compartments play a critical role in the development of Alzheimer's disease (AD), the most common type of senile dementia affecting the elderly. Since insulin-like growth factor II (IGF-II) receptors facilitate the delivery of nascent lysosomal enzymes from the trans-Golgi network to endosomes, we evaluated their role in APP metabolism and cell viability using mouse fibroblast MS cells deficient in the murine IGF-II receptor and corresponding MS9II cells overexpressing the human IGF-II receptors. Our results show that IGF-II receptor overexpression increases the protein levels of APP. This is accompanied by an increase of ␤-site APP-cleaving enzyme 1 levels and an increase of ␤-and ␥-secretase enzyme activities, leading to enhanced A␤ production. At the cellular level, IGF-II receptor overexpression causes localization of APP in perinuclear tubular structures, an increase of lipid raft components, and increased lipid raft partitioning of APP. Finally, MS9II cells are more susceptible to staurosporine-induced cytotoxicity, which can be attenuated by ␤-secretase inhibitor. Together, these results highlight the potential contribution of IGF-II receptor to AD pathology not only by regulating expression/processing of APP but also by its role in cellular vulnerability. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe memory loss followed by the deterioration of higher cognitive functions. Although most cases of AD occur sporadically after the age of 60 years, a small proportion of cases correspond to the early-onset (Ͻ60 years) autosomal dominant form of the disease. To date, mutations in three genes, the amyloid precursor protein (APP) gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14, and the presenilin 2 (PSEN2) gene on chromosome 1, have been identified as the cause of a large proportion of early-onset familial AD (1-3). Additionally, inheritance of the ε4 allele of the apolipoprotein E (APOE) gene on chromosome 19 increases the risk of late-onset and sporadic AD. The neuropathological features associated with AD include the presence of extracellular ␤-amyloid (A␤) peptidecontaining neuritic plaques, intracellular tau-positive neurofibrillary tangles, and the loss of synapses and neurons in defined brain regions. Several lines of in vivo evidence suggest that A␤ peptides initiate or contribute to the neuronal loss and development of AD pathology (2, 4). A␤ peptides are generated from APP, a type I transmembrane protein, which can be processed either by nonamyloidogenic ␣-secretase or amyloidogenic ␤-secretase pathways (5, 6). The ␣-secretase cleaves APP within the A␤ domain, yielding soluble APP␣ and a 10-kDa C-terminal fragment (CTF-␣), which then can be processed by ␥-secretase to generate A␤ 17-40 /A␤ 17-42 fragments. The ␤-secretase, on the other hand, cleaves APP to generate soluble APP␤ and an A␤-containing Cterminal fragment (CTF-␤), which is fu...

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Chapter 24 Insulin‐Like Growth Factor‐2/Mannose‐6 Phosphate Receptors

Cited by 79 publications

References 186 publications

IGF-2R-G_αqsignaling and cardiac hypertrophy in the low-birth-weight lamb

IGF-2R-G_αqsignaling and cardiac hypertrophy in the low-birth-weight lamb

New Biomarkers for Cervical Cancer – Perspectives from the IGF System

Overexpression of the Insulin-Like Growth Factor II Receptor Increases β-Amyloid Production and Affects Cell Viability

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Chapter 24 Insulin‐Like Growth Factor‐2/Mannose‐6 Phosphate Receptors

Cited by 79 publications

References 186 publications

IGF-2R-Gαqsignaling and cardiac hypertrophy in the low-birth-weight lamb

IGF-2R-Gαqsignaling and cardiac hypertrophy in the low-birth-weight lamb

New Biomarkers for Cervical Cancer – Perspectives from the IGF System

Overexpression of the Insulin-Like Growth Factor II Receptor Increases β-Amyloid Production and Affects Cell Viability

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IGF-2R-G_αqsignaling and cardiac hypertrophy in the low-birth-weight lamb

IGF-2R-G_αqsignaling and cardiac hypertrophy in the low-birth-weight lamb