subject predicate object context
44109 Creator d64a4c8b9d6fb32d441f1cd9c453d93b
44109 Creator ext-46a3af38549fa90e5967ca609cf423be
44109 Creator ext-4cb6a4adf9b95c981723b0097d6e8a00
44109 Creator ext-7c1517330626ed42a683b1116c8f4655
44109 Creator ext-9f1cdc097c7abbcf70f7460277ad928c
44109 Creator ext-e9e9dfb58d5f00f53ee2c61dfeee9aab
44109 Date 2006-01-11
44109 Is Part Of repository
44109 Is Part Of p15292401
44109 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.
44109 authorList authors
44109 issue 2
44109 status peerReviewed
44109 volume 26
44109 type AcademicArticle
44109 type Article
44109 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 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
44109 in dataset oro