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Creator |
d64a4c8b9d6fb32d441f1cd9c453d93b |
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Creator |
ext-46a3af38549fa90e5967ca609cf423be |
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Creator |
ext-4cb6a4adf9b95c981723b0097d6e8a00 |
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Creator |
ext-7c1517330626ed42a683b1116c8f4655 |
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Creator |
ext-9f1cdc097c7abbcf70f7460277ad928c |
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Creator |
ext-e9e9dfb58d5f00f53ee2c61dfeee9aab |
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Date |
2006-01-11 |
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Is Part Of |
repository |
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Is Part Of |
p15292401 |
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abstract |
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 Leu<sup>27</sup>IGF-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 Cα(PKCα)-induced phosphorylation
of downstream substrates, myristoylated alanine-rich C kinase substrate, and growth
associated protein-43. Additionally, treatment with Leu<sup>27</sup>IGF-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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authorList |
authors |
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issue |
2 |
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status |
peerReviewed |
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volume |
26 |
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type |
AcademicArticle |
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type |
Article |
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label |
Hawkes, Cheryl ; Jhamandas, Jack H.; Harris, Kim H.; Fu, Wen; MacDonald, Richard
G. and Kar, Satyabrata (2006). 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. Journal of Neuroscience, 26(2) pp. 585–596.
|
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label |
Hawkes, Cheryl ; Jhamandas, Jack H.; Harris, Kim H.; Fu, Wen; MacDonald, Richard G.
and Kar, Satyabrata (2006). 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. Journal of Neuroscience, 26(2) pp. 585–596. |
44109 |
Title |
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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in dataset |
oro |