G-Protein alpha-q signaling cascades
Activated Guanine nucleotide binding protein q receptors
(G-protein alpha-q) receptors
interaction with trimeric G-protein
alpha-q/G-protein beta/gamma causes an
exchange of GDP for GTP bound to G-protein alpha subunits,
and leads to dissociation of the G-protein beta/gamma
heterodimers.
Well-established G-protein alpha-q/11
signaling pathways are activation of Phospholipase C beta
(PLC-beta) and activation, via kinase Bruton
agammaglobulinemia 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) and Diacylglycerol
(DAG). IP3 released into the
cytoplasm mobilizes
Ca('2+)
from internal stores, whereas DAG activates Protein kinase C
epsilon (PKC-epsilon).
PKC-epsilon induces PTK2B protein tyrosine kinase 2 beta
(Pyk2(FAK2)) activation.
PYK2(FAK2)activates V-akt murine thymoma viral oncogene
homolog 1 (AKT(PKB)) through
Phosphoinositide-3-kinase (PI3K)-dependent pathway.
PYK2(FAK2) phosphorylates adaptor protein
Shc and stimulates Growth factor receptor-bound protein 2
(GRB2)/Son of sevenless homolog
(SOS)/v-Ha-ras Harvey rat sarcoma viral oncogene homolog
(H-Ras) signaling cascade.
H-Ras interacts with catalytic subunit of phosphoinositide
3-kinase class 1A (PI3K class 1A), which leads to increase
in phosphoinositide enzymatic activity and catalysis of Phosphatidylinositol
4,5-biphosphate
(PtdIns(4,5)P2),
phosphorylation of which yields Phosphatidylinositol 3,4,5-triphosphate
(PtdIns(3,4,5)P3). Signaling cascade initiated via
G-protein alpha-q and AKT leads
to stimulation of I kappa B kinase (IKK).
IKK phosphorylates nuclear factor of Kappa light polypeptide
gene enhancer in B-cells inhibitor (I-kB) resulting in
dissociation of I-kB from nuclear factor kappa B
(NF-kB) followed by
NF-kB-dependent transcription [1].
G-protein alpha-q directly stimulates Rho
guanine nucleotide exchange factor 12 (LARG).
LARG transforms and activates small G-protein Ras homolog
gene family, member A (RhoA), which participates in
reorganization of cytoskeleton via kinase Rho-associated coiled-coil containing protein
kinase (ROCK) [2].
Regulators of G-protein signaling (RGS) are
GTPase-activating proteins that attenuate signaling by heterotrimeric G-proteins.
RGS2 and RGS3 directly bind
G-protein alpha-q and selectively inhibit
G-protein alpha-q function [3]. Adrenergic beta
receptor kinase 1 (GRK2) binds to the active form of
G-protein alpha-q and leads to selective inhibition of
G-protein alpha-q mediated signaling [4].
References:
- Shi CS, Kehrl JH
PYK2 links G(q)alpha and G(13)alpha signaling to NF-kappa B activation.
The Journal of biological chemistry 2001 Aug 24;276(34):31845-50
- Booden MA, Siderovski DP, Der CJ
Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA.
Molecular and cellular biology 2002 Jun;22(12):4053-61
- Heximer SP
RGS2-mediated regulation of Gqalpha.
Methods in enzymology 2004;390:65-82
- Hains MD, Siderovski DP, Harden TK
Application of RGS box proteins to evaluate G-protein selectivity in receptor-promoted signaling.
Methods in enzymology 2004;389:71-88
