Pathway maps

G-protein signaling_G-Protein alpha-i signaling cascades
G-protein signaling_G-Protein alpha-i signaling cascades

Object List (links open in MetaCore):

G-protein beta/gamma, Caveolin-1, PKA-cat (cAMP-dependent), Adenylate cyclase type I, B-RAF, ATP, RGS18, SOS, 4.6.1.1, RGS11, RGS7, MEK1/2, GRB2, c-SRC, RAP1GAP1, STAT3, G-protein alpha-i family, c-Raf-1, SHC, cAMP, H-Ras, RGS10, RGS14, Erk (MAPK1/3), PKA-reg (cAMP-dependent), RAP-1A

Description

G-Protein alpha-i signaling cascades

Guanine nucleotide binding protein alpha inhibiting activity polypeptide 1 ( G-protein alpha-i ) coupled receptors interact with trimeric G-protein alpha-i/G-protein beta/gamma, which causes exchange of GDP for GTP bound to G protein alpha subunits and dissociation of G-protein beta/gamm a heterodimers.

G-protein alpha-i, directly stimulates kinase activity of tyrosine-protein kinase v-src sarcoma viral oncogene homolog ( c-SRC ) by binding to its catalytic domain and changing conformation of c-SRC. In turn, c-SRC activates v-Ha-ras Harvey rat sarcoma viral oncogene homolog ( H-Ras )/V-raf-1 murine leukemia viral oncogene homolog 1 ( c-Raf-1 )/Mitogen-activated protein kinase kinase 1 and 2 ( MEK1/ 2 )/Mitogen-activated protein kinase 1 and 3 ( Erk (MAPK1/3) ) pathway via phosphorylation of adaptor protein SHC transforming protein 1 ( SHC ) and recruitment of adaptor protein Growth factor receptor-bound protein 2 ( GRB2 ) and positive regulator of RAS guanine nucleotide exchange protein Son of sevenless homolog ( SOS ), leading to cell proliferation and activation of transcription factor signal transducer and activator of transcription 3 ( STAT3 ) [1].

G-protein alpha-i mediates activation of RAP1 GTPase activating protein ( RAP1GAP1 ). RAP1GAP1 transforms RAP1A member of RAS oncogene family ( RAP-1A ) and inhibits V-raf murine sarcoma viral oncogene homolog B1 ( B-RAF )/ MEK1/ 2/ Erk (MAPK1/3) pathway. [2]

G-protein alpha-i inhibits some Adenylate cyclases activity and decreases cAMP concentration in the cell [3].

Regulator of G-protein signaling ( RGS ) proteins are a family of proteins that have been shown to act as GTPase-activating proteins, which attenuate signaling by heterotrimeric G proteins. RGS7, RGS10, RGS11, RGS14, and RGS18 directly bind to G-protein alpha-i and selectively inhibit G protein alpha-i function [4].

Caveolin-1 interacts with G-protein alpha-i subunits and can functionally suppress their activity [5].

References:

  1. Ma YC, Huang XY
    Novel regulation and function of Src tyrosine kinase. Cellular and molecular life sciences : CMLS 2002 Mar;59(3):456-62
  2. Weissman JT, Ma JN, Essex A, Gao Y, Burstein ES
    G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene 2004 Jan 8;23(1):241-9
  3. Defer N, Best-Belpomme M, Hanoune J
    Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase. American journal of physiology. Renal physiology. 2000 Sep;279(3):F400-16
  4. Zhong H, Neubig RR
    Regulator of G protein signaling proteins: novel multifunctional drug targets. The Journal of pharmacology and experimental therapeutics 2001 Jun;297(3):837-45
  5. Minshall RD, Tiruppathi C, Vogel SM, Malik AB
    Vesicle formation and trafficking in endothelial cells and regulation of endothelial barrier function. Histochemistry and cell biology 2002 Feb;117(2):105-12