Activation state-dependent interaction between Gαq subunits and the Fhit tumor suppressor.

Background: The FHIT tumor suppressor gene is arguably the most commonly altered gene in cancer since it is inactivated in about 60% of human tumors. The Fhit protein is a member of the ubiquitous histidine triad proteins which hydrolyze dinucleoside polyphosphates such as Ap3A. Despite the fact that Fhit functions as a tumor suppressor, the pathway through which Fhit inhibits growth of cancer cells remains largely unknown.

Galpha16 activates Ras by forming a complex with tetratricopeptide repeat 1 (TPR1) and Son of Sevenless (SOS).

Many G protein-coupled receptors (GPCRs) are known to modulate cell growth and differentiation by stimulating the extracellular signal-regulated protein kinases (ERKs). In growth factor signaling, ERKs are typically stimulated through an elaborate network of modules consisting of adaptors, protein kinases, and the small GTPase Ras. The mechanism by which G protein signals tap into the ERK signaling pathway has thus far remain elusive.

Galpha16 interacts with Class IA phosphatidylinositol 3-kinases and inhibits Akt signaling.

Phosphatidylinositol 3-kinase (PI3K) mediates receptor tyrosine kinase and G protein coupled receptor (GPCR) signaling by phosphorylating phosphoinositides to elicit various biological responses. Galpha(q) has previously been shown to inhibit class IA PI3K by interacting with the p110alpha subunit. However, it is not known if PI3Ks can associate with other Galpha(q) family members such as Galpha(16).

The RhoA-specific guanine nucleotide exchange factor p63RhoGEF binds to activated Galpha(16) and inhibits the canonical phospholipase Cbeta pathway.

Heterotrimeric G proteins regulate diverse physiological processes by modulating the activities of intracellular effectors. Members of the Galpha(q) family link G protein-coupled receptor activation to phospholipase Cbeta (PLCbeta) activity and intracellular calcium signaling cascades. However, they differ markedly in biochemical properties as well as tissue distribution.

Integration of G protein signals by extracellular signal-regulated protein kinases in SK-N-MC neuroepithelioma cells.

Mammalian cells often receive multiple extracellular stimuli under physiological conditions, and the various signaling inputs have to be integrated for the processing of complex biological responses. G protein-coupled receptors (GPCRs) are critical players in converting extracellular stimuli into intracellular signals. In this report, we examined the integration of different GPCR signals by mitogen-activated protein kinases (MAPKs) using the SK-N-MC human brain neuroepithelioma cells as a neuronal model.