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/gamma 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:
- Ma YC, Huang XY
Novel regulation and function of Src tyrosine kinase.
Cellular and molecular life sciences : CMLS 2002 Mar;59(3):456-62
- 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
- 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
- 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
- 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