Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

G-protein signaling G-Protein beta/gamma signaling cascades


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G-protein signaling G-Protein beta/gamma signaling cascades

G-protein beta/gamma signaling

G proteins are critical cellular signal transducers for a variety ofcell surface receptors. G-protein coupled receptors interact with the trimericG-protein alpha-s/beta/gamma complex and trigger the exchange of GDP to GTP boundto G-protein alpha subunits leading to the dissociation of beta/gammaheterodimers.

Both G-protein alpha and G-protein beta/gamma subunits ofcomplex are able to transduce receptor signaling independently as well. For instance,G-protein beta/gamma subunits regulate caveolae-mediated endocytosis activity andtransendothelial albumin transport via transcytosis by inducing v-src sarcoma(Schmidt-Ruppin A-2) viral oncogene homolog ( c-Src )-mediated tyrosinephosphorylation and subsequent association of endocytic traffic proteins, Caveolin 1,caveolae protein, 22kDa ( Caveolin-1 ) and Dynamin-2 [1].

Another function of G-protein beta/gamma subunits is theactivation of Mitogen-activated protein kinase 1-3 ( ERK1/2 ) pathway via thec-Src activation where c-Src activates ERK1/2 throughphosphorylation of adaptor protein SHC (Src homology 2 domain containing) transformingprotein 1 ( Shc ), and recruitment of adaptor protein Growth factor receptor-boundprotein 2 ( GRB2 ) and Son of sevenless homolog ( SOS ).

G-protein beta/gamma signaling also regulates phosphoinositidemetabolism by increasing the kinase activity of Bruton agammaglobulinemia tyrosine kinase( Btk ), a known activator of Phospholipase C, gamma ( PLC-gamma ) [2] or by direct activation of Phospholipase C, beta 2 ( PLC-beta2 ).PLC-gamma and PLC-beta2 catalyze hydrolysis of phosphoinositide4,5-bisphosphate ( PtdIns(4,5)P2) to form inositol 1,4,5-triphosphate ( IP3) and 1,2-diacyl-glycerol ( DAG ). The G-protein beta/gammaheterodimers also activate Phosphoinositide-3-kinase, regulatory subunit 5 ( PI3K regclass IB (p101) ) that leads to Phosphoinositide-3-kinase, catalytic, gammapolypeptide ( PI3K cat class IB (p110-gamma) ) -mediated conversion ofphosphatidylinositol 4,5-biphosphate ( PtdIns(4,5)P2 ) to phosphatidylinositol3,4,5-triphosphate ( PtdIns(3,4,5)P3 ) [3]. PtdIns(3,4,5)P3 isa 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[4].

G-proteins beta/gamma can regulate Adenylate cyclase 2 ( Adenylate cyclasetype II ) and Adenylate cyclase 5 ( Adenylate cyclase type V ) activity.Adenylate cyclases increase level of cAMP in cells and activate Proteinkinase, cAMP-dependent, regulatory ( PKA-reg (cAMP-dependent) ) that results inProtein kinase, cAMP-dependent, catalytic ( PKA-cat (cAMP-dependent) ) activation[5].

Regulator of G-protein signaling 3 ( RGS3 ) binds G-proteinbeta/gamma subunits and limits their ability to trigger the production of inositolphosphates and the activation of AKT(PKB) and ERK1/2 signaling [6].