Disease relevance of GNAQ

• Although both G alpha and G beta gamma G protein subunits have been shown to activate purified PLC beta in vitro, G alpha q has been presumed to mediate the pertussis toxin-insensitive response in vivo [1].
• Signal transduction during cardiac hypertrophy: the role of G alpha q, PLC beta I, and PKC [2].
• Genomic sequence analysis of a key residue (Arg183) in human G alpha q in invasive non-functional pituitary adenomas [3].
• Intracellular 50 microM inositol 1,4,5-trisphosphate (1,4,5 InsP(3)) also induced the inward current in five (38%) of 13 rod cells, but intracellular Pasteurella multocida toxin (5 microg/mL, G alpha q-coupled PLC activator) did not elicit any response in the cells [4].
• Since altered expression/activity of Galphaq is implicated in heart disease, we re-sequenced the GNAQ promoter in 1052 prospectively followed heart failure patients [5].

Psychiatry related information on GNAQ

• Increased G alpha q/11 immunoreactivity in postmortem occipital cortex from patients with bipolar affective disorder [6].
• As disturbances in guanine nucleotide binding (G) protein-coupled phosphoinositide second messenger systems have been implicated in bipolar disorder, we examined whether the abundance of G alpha q/11 and phospholipase C (PLC)-beta 1 two key transducing proteins in this signaling pathway, are altered in this disorder [6].
• Phosphoinositide hydrolysis, G alpha q, phospholipase C, and protein kinase C in post mortem human brain: effects of post mortem interval, subject age, and Alzheimer's disease [7].
• Girls completed on two occasions a 24-h physical activity checklist of yesterday and usual activities, including sedentary activities (GEMS Activity Questionnaire, GAQ), and a 3-d computerized self-report instrument (Activitygram) [8].

High impact information on GNAQ

• However, reconstitution was not observed with cells that overexpressed G alpha q or G alpha 11 [9].
• Further evaluation revealed that GRP-R in these cells tonically stimulated G alpha q/11, resulting in increased phospholipase C activation [10].
• These data indicate that G alpha s, G alpha q/11, and G alpha i3 associate with Golgi membranes independent of G beta subunits and have distinctive distributions within the Golgi stack [11].
• METHODS: We used selective antibodies to quantitate the levels of the G protein alpha subunits that regulate adenylate cyclase activity (G alpha s and G alpha i2) and phosphoinositide turnover (G alpha q/11) [12].
• There were no significant differences in the immunolabeling of G alpha i1/2, G alpha q/11, or pertussis toxin-catalyzed [32P]ADP ribosylation in either tissue in the untreated bipolar affective disorder group compared with controls [12].

Chemical compound and disease context of GNAQ

• Like the latter proteins, the Lymnaea G alpha q C-terminus lacks a cysteine that could serve as a substrate for pertussis toxin [13].
• In both tissues, lithium-treated subjects demonstrated lower levels of G alpha q/11 and higher levels of pertussis toxin-catalyzed [32P]ADP-ribosylation, which reached significance in the platelet membranes [12].

Biological context of GNAQ

• Specificity of G alpha q and G alpha 11 gene expression in platelets and erythrocytes. Expressions of cellular differentiation and species differences [14].
• To define their roles in platelet activation we studied G alpha q and G alpha 11 gene expression by immunotransfer blotting and by reverse transcription of mRNA followed by PCR (RT-PCR) and direct sequencing [14].
• Antisense nucleotides and antibodies to G alpha q/11 blocked the m3-mediated signal transduction by inhibiting interaction of the muscarinic receptor with the G protein [1].
• Agonist stimulation causes tubulin association with the plasma membrane and activation of PLC beta 1 through direct interaction with, and transactivation of, G alpha q [15].
• High efficiency transient transfection of Cos-7 cells was previously used to establish the functional coupling between G alpha q/G alpha 11 and phospholipase C beta 1 (Wu, D., Lee, C-H., Rhee, S. G., and Simon, M. I. (1992) J. Biol. Chem. 267, 1811-1817) [16].

Anatomical context of GNAQ

• Activation of platelet-activating factor receptor-coupled G alpha q leads to stimulation of Src and focal adhesion kinase via two separate pathways in human umbilical vein endothelial cells [17].
• The cotransfection of Cos-7 cells with cDNAs encoding three different alpha 1-adrenergic receptors and G alpha q or G alpha 11 leads to an increase in norepinephrine-dependent inositol phosphate release [16].
• We conclude that receptor coupling specificity of the G alpha q/G beta gamma heterotrimer is determined by G alpha q; G beta gamma is the predominant signaling molecule activating oocyte PLC beta [1].
• We report that human myometrium contains G alpha i1, G alpha i3, and G alpha q, and G alpha 11, which are expressed at similar levels in tissues from pregnant and nonpregnant women [18].
• Specifically, G alpha i2, G alpha i3, G alpha o, G alpha s, and G alpha q/11 levels reached 87%, 81%, 91%, 99%, and 103% respectively of those from normal placentas [19].

Associations of GNAQ with chemical compounds

• Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists [20].
• RT-PCR performed with gene-specific primers demonstrated G alpha q mRNA, but not G alpha 11 mRNA, in normal human and mouse platelets and in thromboxane-sensitive and thromboxane-insensitive dog platelets [14].
• Platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors activate PI-PLC via G alpha q, but the role of G alpha 11 is uncertain [14].
• Purified G beta gamma, alone or with phosphatidylinositol 4,5-bisphosphate (PIP2), inhibited carbachol-evoked membrane recruitment of tubulin and G alpha q transactivation by tubulin [15].
• Expression of angiotensin II type-I receptor and phospholipase C-linked G alpha q/11 protein in the human placenta [21].

Physical interactions of GNAQ

• Several lines of evidence indicate that the oxytocin receptor is functionally coupled to GTP-binding proteins of the G alpha q/11 class which stimulate phospholipase C activity [22].

Regulatory relationships of GNAQ

• GNAZ is expressed in high levels in neural tissue while GNAQ is ubiquitously expressed [23].
• The stimulation by oxytocin of phosphoinositide turnover in COS cells transfected with a plasmid expressing the oxytocin receptor is enhanced by cotransfection of G alpha q [22].

Other interactions of GNAQ

• G protein-coupled receptor Kinase 2/G alpha q/11 interaction. A novel surface on a regulator of G protein signaling homology domain for binding G alpha subunits [24].
• Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 and G alpha q [25].
• Furthermore, the exchange of a few carboxyl-terminal residues of G alpha q by those of G alpha 12 or G alpha o allows the resulting chimeric G alpha subunits (G alpha ql and G alpha qol respectively) to couple Gi-coupled receptors to PLC [20].
• RESULTS: Using this setup we successfully amplified and sequenced GC-rich DNA regions such as the 5'-upstream regions of the genes GNAS1 and GNAQ as well as exon1 of the BRAF gene which could not be amplified by others [26].
• Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s, or thyrotropin-releasing hormone receptor genes [27].

Analytical, diagnostic and therapeutic context of GNAQ

• Immunoblotting studies of the platelet membrane fractions, quantified by densitometric analysis, showed that levels of the G alpha q subunit were not significantly different between adult and neonate, and were not the cause of the marked differences in GTPase activity [28].
• METHODS: Western blot analysis of placental membrane proteins was performed using a chemiluminescence kit and specific antibodies against AT1 receptor and G alpha q/11 protein [21].
• Northern blot analyses of AT1 receptor and G alpha q/11 mRNA expression were accomplished using random primed [32P]dCTP-labeled specific probes [21].
• In situ hybridization reveals G alpha q-encoding mRNA(s) to be present throughout the CNS [13].
• Through molecular cloning we have identified a molluscan G protein alpha subunit which belongs to the G alpha q family and is expressed in the central nervous system (CNS) of the pond snail, Lymnaea stagnalis [13].

References