Pathway Map Details
G-protein signaling_G-Protein beta/gamma signaling cascades
Object list (links open in MetaCore):
G-protein beta/gamma, PKA-reg (cAMP-dependent), PLC-beta2, SHC, PLC-gamma, AKT(PKB), 18.104.22.168, H-Ras, 22.214.171.124, IP3, Dynamin-2, PI3K cat class IB (p110-gamma), DAG, Adenylate cyclase type V, c-SRC, Adenylate cyclase type II, Btk, PKA-cat (cAMP-dependent), 126.96.36.199, G-protein alpha-15, MEK1/2, Erk (MAPK1/3), PDK (PDPK1), PI(3,4,5)P3, GRB2, Caveolin-1, PI(4,5)P2, SOS, PI3K reg class IB (p101), ATP, RGS3, cAMP
G-protein beta/gamma signaling
G proteins are critical cellular signal transducers for a variety of cell surface receptors. G-protein coupled receptors interact with the trimeric G-protein alpha-s/beta/gamma complex and trigger the exchange of GDP to GTP bound to G-protein alpha subunits leading to the dissociation of beta/gamma heterodimers.
Both G-protein alpha and G-protein beta/gamma subunits of complex are able to transduce receptor signaling independently as well. For instance, G-protein beta/gamma subunits regulate caveolae-mediated endocytosis activity and transendothelial albumin transport via transcytosis by inducing v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog ( c-Src )-mediated tyrosine phosphorylation and subsequent association of endocytic traffic proteins, Caveolin 1, caveolae protein, 22kDa ( Caveolin-1 ) and Dynamin-2 .
Another function of G-protein beta/gamma subunits is the activation of Mitogen-activated protein kinase 1-3 ( ERK1/2 ) pathway via the c-Src activation where c-Src activates ERK1/2 through phosphorylation of adaptor protein SHC (Src homology 2 domain containing) transforming protein 1 ( Shc ), and recruitment of adaptor protein Growth factor receptor-bound protein 2 ( GRB2 ) and Son of sevenless homolog ( SOS ).
G-protein beta/gamma signaling also regulates phosphoinositide metabolism by increasing the kinase activity of Bruton agammaglobulinemia tyrosine kinase ( Btk ), a known activator of Phospholipase C, gamma ( PLC-gamma )  or by direct activation of Phospholipase C, beta 2 ( PLC-beta2 ). PLC-gamma and PLC-beta2 catalyze hydrolysis of phosphoinositide 4,5-bisphosphate ( PtdIns(4,5)P2) to form inositol 1,4,5-triphosphate ( IP3 ) and 1,2-diacyl-glycerol ( DAG ). The G-protein beta/gamma heterodimers also activate Phosphoinositide-3-kinase, regulatory subunit 5 ( PI3K reg class IB (p101) ) that leads to Phosphoinositide-3-kinase, catalytic, gamma polypeptide ( PI3K cat class IB (p110-gamma) ) -mediated conversion of phosphatidylinositol 4,5-biphosphate ( PtdIns(4,5)P2 ) to phosphatidylinositol 3,4,5-triphosphate ( PtdIns(3,4,5)P3 ) . PtdIns(3,4,5)P3 is a second messenger that directly binds to 3-phosphoinositide dependent protein kinase-1 ( PDK(PDPK1) ) and V-akt murine thymoma viral oncogene homolog 1 ( AKT(PKB) ). PDK(PDPK1) phosphorylates AKT(PKB) and activates AKT signaling .
G-proteins beta/gamma can regulate Adenylate cyclase 2 ( Adenylate cyclase type II ) and Adenylate cyclase 5 ( Adenylate cyclase type V ) activity. Adenylate cyclases increase level of cAMP in cells and activate Protein kinase, cAMP-dependent, regulatory ( PKA-reg (cAMP-dependent) ) that results in Protein kinase, cAMP-dependent, catalytic ( PKA-cat (cAMP-dependent) ) activation .
Regulator of G-protein signaling 3 ( RGS3 ) binds G-protein beta/gamma subunits and limits their ability to trigger the production of inositol phosphates and the activation of AKT(PKB) and ERK1/2 signaling .
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