G-protein signaling G-Protein alpha-q signaling cascades
G-Protein alpha-q signaling cascades Activated Guanine nucleotide binding protein q receptors ( G-proteinalpha-q ) receptors interaction with trimeric G-protein alpha-q/G-protein beta/gamma causes an exchange of GDP for GTP bound to G-proteinalpha subunits, and leads to dissociation of the G-protein beta/gammaheterodimers. Well-established G-protein alpha-q/11 signaling pathways areactivation of Phospholipase C beta ( PLC-beta ) and activation, via kinase Brutonagammaglobulinemia tyrosine kinase ( Btk ), of Phospholipase C gamma (PLC-gamma ), which catalyzes hydrolysis of Phosphoinositide 4,5-bisphosphate (PtdIns(4,5)P2 ) to form Inositol 1,4,5-triphosphate ( IP3 ) andDiacylglycerol ( DAG ). IP3 released into the cytoplasm mobilizesCa( ' 2+) from internal stores, whereas DAG activates Protein kinaseC epsilon ( PKC-epsilon ). PKC-epsilon induces PTK2B protein tyrosinekinase 2 beta ( Pyk2(FAK2) ) activation. PYK2(FAK2) activates V-akt murinethymoma viral oncogene homolog 1 ( AKT(PKB) ) through Phosphoinositide-3-kinase (PI3K )-dependent pathway. PYK2(FAK2) phosphorylates adaptor proteinShc and stimulates Growth factor receptor-bound protein 2 ( GRB2 )/ S on ofsevenless homolog ( SOS )/v-Ha-ras Harvey rat sarcoma viral oncogene homolog (H-Ras ) signaling cascade. H-Ras interacts with catalytic subunit ofphosphoinositide 3-kinase class 1A ( PI3K class 1A ), which leads to increase inphosphoinositide enzymatic activity and catalysis of Phosphatidylinositol 4,5-biphosphate( PtdIns(4,5)P2 ) , phosphorylation of which yields Phosphatidylinositol3,4,5-triphosphate ( PtdIns(3,4,5)P3 ). Signaling cascade initiated viaG-protein alpha-q and AKT leads to stimulation of I kappa B kinase (IKK ). IKK phosphorylates nuclear factor of Kappa light polypeptide geneenhancer in B-cells inhibitor ( I-kB ) resulting in dissociation of I-kBfrom nuclear factor kappa B ( NF-kB ) followed by NF-kB -dependenttranscription . G-protein alpha-q directly stimulates Rho guanine nucleotideexchange factor 12 ( LARG ). LARG transforms and activates small G-proteinRas homolog gene family, member A ( RhoA ), which participates in reorganizationof cytoskeleton via kinase Rho-associated coiled-coil containing protein kinase (ROCK ) . Regulators of G-protein signaling ( RGS ) are GTPase-activatingproteins that attenuate signaling by heterotrimeric G-proteins. RGS2 andRGS3 directly bind G-protein alpha-q and selectively inhibit G-proteinalpha-q function . Adrenergic beta receptor kinase 1 ( GRK2 )binds to the active form of G-protein alpha-q and leads to selective inhibition ofG-protein alpha-q mediated signaling .