Gq/n proteins

Mi Nerves Seven transmembrane segments, Gq/n protein-linked IP3, DAG cascade... 

Cox SL, Schelb V, Trendelenburg AU, Starke K (2000) Enhancement of noradrenaline release by angiotensin II and bradykinin in mouse atria evidence for cross-talk between Gq/n protein and Gj/0 protein-coupled receptors. BrJ Pharmacol 129 1095-1102 Craig TJ, Evans GJ, Morgan A (2003) Physiological regulation of Muncl8/nSecl phosphorylation on serine-313. J Neurochem 86 1450-7... 

Fig. 3 Mechanisms involved in presynaptic inhibition through P2Y receptors. P2Yi 2,4,12 receptors may couple to PTX-sensitive proteins and mediate voltage-dependent inhibition of calcium currents by direct interaction of the Py subunits with the N-type VSCC (1). The P2Yi, 2,4 receptor subtypes may also couple to PTX-insensitive Gq/n proteins and mediate voltage-independent inhibition of Ca2+ currents by (2) direct interaction of G protein Py subunits with the channel or (3) activation of phospholipase C (PLC), causing depletion of membrane phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).

Stimulation of the oti-adrenoreceptors results in the activation of the Gq/n protein, which subsequently activates phospholipase CP (PLCP) and leads to cleavage of phosphatidylinositol-4,5-bisphosphate into inositol-1,4,5-trisphosphate (IP3) and... 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

Fig. 11.1 Activation of MAPK pathway by Angll and ET-1 in VSMC. Stimulation of Angll and ET-1 receptors through Gq/n activation enhances the activity of PLCp. Activated PLC 3 converts PIP2 to IP3 and diacylglycerol (DAG). IP3 elevates the concentration of intracellular calcium and DAG activates PKC. PKC and/or Ca2+/calmodulin (CaM)-dependent protein kinases (CaMK) activate nonreceptor (NR) and/or receptor (R) protein tyrosine kinases. Activation of these components signals the stimulation of Ras/Raf/MEK/ERKl/2 and p70 s6k. ERK1/2 and p70 s6k are translocated to nucleus and regulate nuclear events by activating transcription factors through phosphorylation.

There are three distinct mammalian tachykinin receptors, termed NK, NK2 and NKj, all of which are of the 7-transmembrane G-protein-coupled superfamily, and which couple via the InsP DAG (Gq/n) pathway. These are produced by three or more separate genes. The orders of potency of the three principal endogenous peptides at the three receptors are as follows at NK, receptors, SP > NKA > NKB At NK2 receptors, NKA > NKB SP at NK3 receptors, NKB > NKA > SP. Thus each agonist can act at each receptor. 

N-terminal 21 amino adds of the i3 loop were replaced with m3 sequence (Emax ca. 40% of vdld type m3 Fig. 7). This finding clearly indicates that the i2 loop also makes a critical contribution to proper recognition of Gq/11 proteins. 

Figure 11. Residues in the m3 mAChR (rat) critically involved in selective recognition of Gq/il [39]. Only the intracellular receptor regions and a few amino acids of TM I-VII are shown. Besides the nine amino acids highlighted in black, optimum activation of Gq/11 proteins appears to require one or more additional residues in the N-terminal portion of the i3 loop (stippled sequence ref. 39).

---