دورية أكاديمية
Receptor for activated C kinase-1 facilitates protein kinase C-dependent phosphorylation and functional modulation of GABA(A) receptors with the activation of G-protein-coupled receptors
| العنوان: | Receptor for activated C kinase-1 facilitates protein kinase C-dependent phosphorylation and functional modulation of GABA(A) receptors with the activation of G-protein-coupled receptors |
|---|---|
| المؤلفون: | Brandon, NJ, Jovanovic, JN, Smart, TG, Moss, SJ |
| المصدر: | J NEUROSCI , 22 (15) 6353 - 6361. (2002) |
| بيانات النشر: | SOC NEUROSCIENCE |
| سنة النشر: | 2002 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | GABA(A) receptor, protein kinase C, receptor for activated C kinase, muscarinic receptor phosphorylation, cross talk, GST fusion protein, A RECEPTOR, BETA-SUBUNIT, INTRACELLULAR DOMAINS, CORTICAL-NEURONS, TYROSINE KINASES, ION CHANNELS, RACK1, SITES, EXPRESSION, INTERACTS |
| الوصف: | GABA(A) receptors are the principal sites of fast synaptic inhibition in the brain. These receptors are hetero-pentamers that can be assembled from a number of subunit classes: alpha(1-6), beta(1-3), gamma(1-3), delta(1), epsilon, theta, and pi, but the majority of receptor subtypes is believed, however, to be composed of alpha, beta, and gamma2 subunits. A major mechanism for modulating GABA(A) receptor function occurs via the phosphorylation of residues within the intracellular domains of receptor subunits by a range of serine/ threonine and tyrosine kinases. However, how protein kinases are targeted to these receptors to facilitate functional modulation remains unknown. Here we demonstrate that the receptor for activated C kinase (RACK-1) and protein kinase C (PKC) bind to distinct sites on GABA(A) receptor beta subunits. Although RACK-1 is not essential for PKC binding to GABAA receptor beta subunits, it enhances the phosphorylation of serine 409, a residue critical for the phospho-dependent modulation of GABA(A) receptor function in the beta1 subunit by anchored PKC. Furthermore, RACK-1 also enhances GABA(A) receptor functional modulation in neurons by a PKC-dependent signaling pathway with the activation of muscarinic acetylcholine receptors (mAChRs). This PKC-dependent modulation of neuronal GABAA receptors was mirrored by an increase in the phosphorylation of GABA(A) receptor beta subunits with the activation of mAChRs.Our results suggest a central role for RACK-1 in potentiating PKC-dependent phosphorylation and functional modulation of GABA(A) receptors. Therefore, RACK-1 will enhance functional cross talk between GABA(A) receptors and G-protein-coupled receptors and therefore may have profound effects on neuronal excitability. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/83637/1/receptor.pdfTest; https://discovery.ucl.ac.uk/id/eprint/83637Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/83637/1/receptor.pdfTest https://discovery.ucl.ac.uk/id/eprint/83637Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.D75A75DE |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |