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rdf:type |
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lifeskim:mentions |
umls-concept:C0021666,
umls-concept:C0033640,
umls-concept:C0123711,
umls-concept:C0205099,
umls-concept:C0205171,
umls-concept:C0542341,
umls-concept:C0599668,
umls-concept:C0851285,
umls-concept:C1519623,
umls-concept:C1704259,
umls-concept:C1705987
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pubmed:issue |
2
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pubmed:dateCreated |
2006-1-12
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pubmed:abstractText |
The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a single-pass transmembrane glycoprotein that plays an important role in the intracellular trafficking of lysosomal enzymes and endocytosis-mediated degradation of IGF-II. However, its role in signal transduction after IGF-II binding remains unclear. In the present study, we report that IGF-II/M6P receptor in the rat brain is coupled to a G-protein and that its activation by Leu27IGF-II, an analog that binds rather selectively to the IGF-II/M6P receptor, potentiates endogenous acetylcholine release from the rat hippocampal formation. This effect is mediated by a pertussis toxin (PTX)-sensitive GTP-binding protein and is dependent on protein kinase Calpha (PKCalpha)-induced phosphorylation of downstream substrates, myristoylated alanine-rich C kinase substrate, and growth associated protein-43. Additionally, treatment with Leu27IGF-II causes a reduction in whole-cell currents and depolarization of cholinergic basal forebrain neurons. This effect, which is blocked by an antibody against the IGF-II/M6P receptor, is also sensitive to PTX and is mediated via activation of a PKC-dependent pathway. These results together revealed for the first time that the single transmembrane domain IGF-II/M6P receptor expressed in the brain is G-protein coupled and is involved in the regulation of central cholinergic function via the activation of specific intracellular signaling cascades.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Delayed Rectifier Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/GAP-43 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha Subunit...,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Guanylyl Imidodiphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/iberiotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/insulin-like growth factor II...,
http://linkedlifedata.com/resource/pubmed/chemical/myristoylated alanine-rich C...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
585-96
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16407557-Acetylcholine,
pubmed-meshheading:16407557-Amino Acid Substitution,
pubmed-meshheading:16407557-Animals,
pubmed-meshheading:16407557-Binding, Competitive,
pubmed-meshheading:16407557-Cholera Toxin,
pubmed-meshheading:16407557-Delayed Rectifier Potassium Channels,
pubmed-meshheading:16407557-GAP-43 Protein,
pubmed-meshheading:16407557-GTP-Binding Protein alpha Subunit, Gi2,
pubmed-meshheading:16407557-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:16407557-Guanylyl Imidodiphosphate,
pubmed-meshheading:16407557-Hippocampus,
pubmed-meshheading:16407557-Insulin,
pubmed-meshheading:16407557-Insulin-Like Growth Factor I,
pubmed-meshheading:16407557-Insulin-Like Growth Factor II,
pubmed-meshheading:16407557-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16407557-Isoproterenol,
pubmed-meshheading:16407557-Male,
pubmed-meshheading:16407557-Membrane Proteins,
pubmed-meshheading:16407557-Nerve Tissue Proteins,
pubmed-meshheading:16407557-Neurons,
pubmed-meshheading:16407557-Patch-Clamp Techniques,
pubmed-meshheading:16407557-Peptides,
pubmed-meshheading:16407557-Pertussis Toxin,
pubmed-meshheading:16407557-Potassium Channel Blockers,
pubmed-meshheading:16407557-Potassium Channels, Calcium-Activated,
pubmed-meshheading:16407557-Protein Kinase C-alpha,
pubmed-meshheading:16407557-Rats,
pubmed-meshheading:16407557-Rats, Sprague-Dawley,
pubmed-meshheading:16407557-Receptor, IGF Type 2,
pubmed-meshheading:16407557-Receptors, G-Protein-Coupled,
pubmed-meshheading:16407557-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16407557-Signal Transduction
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pubmed:year |
2006
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pubmed:articleTitle |
Single transmembrane domain insulin-like growth factor-II/mannose-6-phosphate receptor regulates central cholinergic function by activating a G-protein-sensitive, protein kinase C-dependent pathway.
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pubmed:affiliation |
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, H3A 2B4, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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