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Single-transmembrane domain IGF-II/M6P receptor: Potential interaction with g protein and its association with cholesterol-rich membrane domains

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Single-transmembrane domain IGF-II/M6P receptor : Potential interaction with g protein and its association with cholesterol-rich membrane domains. / Amritraj, Asha; Posse De Chaves, Elena I.; Hawkes, Cheryl; MacDonald, Richard G.; Kar, Satyabrata.

In: Endocrinology, Vol. 153, No. 10, 01.10.2012, p. 4784-4798.

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Amritraj, Asha ; Posse De Chaves, Elena I. ; Hawkes, Cheryl ; MacDonald, Richard G. ; Kar, Satyabrata. / Single-transmembrane domain IGF-II/M6P receptor : Potential interaction with g protein and its association with cholesterol-rich membrane domains. In: Endocrinology. 2012 ; Vol. 153, No. 10. pp. 4784-4798.

Bibtex

@article{80a8e845ac054dd9a46ca66b96c2c5a9,
title = "Single-transmembrane domain IGF-II/M6P receptor: Potential interaction with g protein and its association with cholesterol-rich membrane domains",
abstract = "The IGF-II/mannose 6-phosphate (M6P) receptor is a single-transmembrane domain glycoprotein that plays an important role in the intracellular trafficking of lysosomal enzymes and endocytosis-mediated degradation of IGF-II. The receptor may also mediate certain biological effects in response to IGF-II binding by interacting with G proteins. However, the nature of the IGF-II/M6P receptor's interaction with the G protein or with G protein-coupled receptor (GPCR) interacting proteins such as β-arrestin remains unclear. Here we report that [125I]IGF-II receptor binding in the rat hippocampal formation is sensitive to guanosine-5′-[γ-thio]triphosphate, mastoparan, and Mas-7, which are known to interfere with the coupling of the classical GPCR with G protein. Monovalent and divalent cations also influenced [125I]IGF-II receptor binding. The IGF-II/M6P receptor, as observed for several GPCRs, was found to be associated with β-arrestin 2, which exhibits sustained ubiquitination after stimulation with Leu27IGF-II, an IGF-II analog that binds rather selectively to the IGF-II/M6P receptor. Activation of the receptor by Leu27IGF-II induced stimulation of extracellular signal-related kinase 1/2 via a pertussis toxin-dependent pathway. Additionally, we have shown that IGF-II/M6P receptors under normal conditions are associated mostly with detergent- resistant membrane domains, but after stimulation with Leu27IGF-II, are translocated to the detergent-soluble fraction along with a portion of β-arrestin 2. Collectively these results suggest that the IGF-II/M6P receptor may interact either directly or indirectly with G protein as well as β-arrestin 2, and activation of the receptor by an agonist can lead to alteration in its subcellular distribution along with stimulation of an intracellular signaling cascade.",
author = "Asha Amritraj and {Posse De Chaves}, {Elena I.} and Cheryl Hawkes and MacDonald, {Richard G.} and Satyabrata Kar",
year = "2012",
month = oct,
day = "1",
doi = "10.1210/en.2012-1139",
language = "English",
volume = "153",
pages = "4784--4798",
journal = "Clinical Endocrinology",
issn = "0300-0664",
publisher = "Wiley-Blackwell",
number = "10",

}

RIS

TY - JOUR

T1 - Single-transmembrane domain IGF-II/M6P receptor

T2 - Potential interaction with g protein and its association with cholesterol-rich membrane domains

AU - Amritraj, Asha

AU - Posse De Chaves, Elena I.

AU - Hawkes, Cheryl

AU - MacDonald, Richard G.

AU - Kar, Satyabrata

PY - 2012/10/1

Y1 - 2012/10/1

N2 - The IGF-II/mannose 6-phosphate (M6P) receptor is a single-transmembrane domain glycoprotein that plays an important role in the intracellular trafficking of lysosomal enzymes and endocytosis-mediated degradation of IGF-II. The receptor may also mediate certain biological effects in response to IGF-II binding by interacting with G proteins. However, the nature of the IGF-II/M6P receptor's interaction with the G protein or with G protein-coupled receptor (GPCR) interacting proteins such as β-arrestin remains unclear. Here we report that [125I]IGF-II receptor binding in the rat hippocampal formation is sensitive to guanosine-5′-[γ-thio]triphosphate, mastoparan, and Mas-7, which are known to interfere with the coupling of the classical GPCR with G protein. Monovalent and divalent cations also influenced [125I]IGF-II receptor binding. The IGF-II/M6P receptor, as observed for several GPCRs, was found to be associated with β-arrestin 2, which exhibits sustained ubiquitination after stimulation with Leu27IGF-II, an IGF-II analog that binds rather selectively to the IGF-II/M6P receptor. Activation of the receptor by Leu27IGF-II induced stimulation of extracellular signal-related kinase 1/2 via a pertussis toxin-dependent pathway. Additionally, we have shown that IGF-II/M6P receptors under normal conditions are associated mostly with detergent- resistant membrane domains, but after stimulation with Leu27IGF-II, are translocated to the detergent-soluble fraction along with a portion of β-arrestin 2. Collectively these results suggest that the IGF-II/M6P receptor may interact either directly or indirectly with G protein as well as β-arrestin 2, and activation of the receptor by an agonist can lead to alteration in its subcellular distribution along with stimulation of an intracellular signaling cascade.

AB - The IGF-II/mannose 6-phosphate (M6P) receptor is a single-transmembrane domain glycoprotein that plays an important role in the intracellular trafficking of lysosomal enzymes and endocytosis-mediated degradation of IGF-II. The receptor may also mediate certain biological effects in response to IGF-II binding by interacting with G proteins. However, the nature of the IGF-II/M6P receptor's interaction with the G protein or with G protein-coupled receptor (GPCR) interacting proteins such as β-arrestin remains unclear. Here we report that [125I]IGF-II receptor binding in the rat hippocampal formation is sensitive to guanosine-5′-[γ-thio]triphosphate, mastoparan, and Mas-7, which are known to interfere with the coupling of the classical GPCR with G protein. Monovalent and divalent cations also influenced [125I]IGF-II receptor binding. The IGF-II/M6P receptor, as observed for several GPCRs, was found to be associated with β-arrestin 2, which exhibits sustained ubiquitination after stimulation with Leu27IGF-II, an IGF-II analog that binds rather selectively to the IGF-II/M6P receptor. Activation of the receptor by Leu27IGF-II induced stimulation of extracellular signal-related kinase 1/2 via a pertussis toxin-dependent pathway. Additionally, we have shown that IGF-II/M6P receptors under normal conditions are associated mostly with detergent- resistant membrane domains, but after stimulation with Leu27IGF-II, are translocated to the detergent-soluble fraction along with a portion of β-arrestin 2. Collectively these results suggest that the IGF-II/M6P receptor may interact either directly or indirectly with G protein as well as β-arrestin 2, and activation of the receptor by an agonist can lead to alteration in its subcellular distribution along with stimulation of an intracellular signaling cascade.

U2 - 10.1210/en.2012-1139

DO - 10.1210/en.2012-1139

M3 - Journal article

C2 - 22903618

AN - SCOPUS:84866751138

VL - 153

SP - 4784

EP - 4798

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 10

ER -