Gq subfamily

The members of the Gq subfamily are not modifiable by pertussis toxin or cholera toxin. The signal protein next in the reaction sequence is generally the /1-type of phospholipase C. 

ANGII, ai-adrenergic agonists and endothelin-1 are relevant stimulants of PLC p isozymes via the a subunits of the heterotrimeric Gq subfamily PLC p has also been shown to be activated by Gpy dimer (Lee et al., 1994). A nontyrosine kinase activation of PLC y isozymes has been reported (Rhee and Bae,... 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

So far four G protein subfamilies have been identified and classified according to the more than 20 known a subunits (Gq/11, Gi/0, Gs, and G12/13) [6]. There is a similar variety of beta and gamma subunits. G proteins can act either stimulatory or inhibitory. 

It has now been established by studies of numerous tissues that the interaction of all members of the Nk receptor family with appropriate ligands results in G protein-linked activation of phospholipase C and phos-phoinositol turnover with increased synthesis of inositol triphosphate (IPs) and consequent increases in levels of intracellular calcium (Nakanishi et al., 1993). This activation occurs via a pertussis toxin-insensitive pathway and probably involves the Gq/11 subfamily of Ga proteins (Kwatra et al., 1993). Activation of transfected tachykinin receptors in CHO cells can also result in the generation of cAMP (Nakajima et al., 1992 Wiener, 1993). 

In most cases, it has been found that each member of an AR subfamily couples faithfully to a single G protein type. The arARs (a1A, a1B, a1D) act through Gq/11 to increase intracellular Ca2+, 0(2-ARs (o a, a2 S, oc ) act through G to decrease cAMP, and P-ARs (Pj, P2, P3) act through Gs to increase cAMP. The dual G protein specificity observed with other GPCRs, such as angiotensin II receptors (which activate both Gq/11 and G, families) (7), has not generally been observed with AR subtypes. 

Within the subfamily of prostanoid receptors that are linked to calcium increments, the EP3 subtype stands out for a notable feature the promiscuity of its coupling to intracellular second messengers. Like other members of its subfamily, the EP3 receptor can activate a Gq protein and elicit calcium rises, which are thought to underlie biological responses such as smooth muscle contraction. But the EP3 receptors can be also linked to the inhibition of adenylate cyclase activity. This effect, mediated via Gi, may be responsible for the reduction of acid secretion produced by PGE2 in gastric mucosa. Finally, in some tissues, EP3 receptor stimulation may also result in the activation of adenylate cyclase. 

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